| 1. |
- Namkoong, H, et al.
(författare)
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DOCK2 is involved in the host genetics and biology of severe COVID-19
- 2022
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 609:7928, s. 754-
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Tidskriftsartikel (refereegranskat)abstract
- Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge1–5. Here we conducted a genome-wide association study (GWAS) involving 2,393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3,289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target.
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| 2. |
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| 3. |
- Wang, QBS, et al.
(författare)
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The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force
- 2022
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1, s. 4830-
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Tidskriftsartikel (refereegranskat)abstract
- Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection.
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| 4. |
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| 5. |
- Forrest, ARR, et al.
(författare)
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A promoter-level mammalian expression atlas
- 2014
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 507:7493, s. 462-
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Tidskriftsartikel (refereegranskat)
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| 6. |
- Noguchi, S, et al.
(författare)
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FANTOM5 CAGE profiles of human and mouse samples
- 2017
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Ingår i: Scientific data. - : Springer Science and Business Media LLC. - 2052-4463. ; 4, s. 170112-
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Tidskriftsartikel (refereegranskat)abstract
- In the FANTOM5 project, transcription initiation events across the human and mouse genomes were mapped at a single base-pair resolution and their frequencies were monitored by CAGE (Cap Analysis of Gene Expression) coupled with single-molecule sequencing. Approximately three thousands of samples, consisting of a variety of primary cells, tissues, cell lines, and time series samples during cell activation and development, were subjected to a uniform pipeline of CAGE data production. The analysis pipeline started by measuring RNA extracts to assess their quality, and continued to CAGE library production by using a robotic or a manual workflow, single molecule sequencing, and computational processing to generate frequencies of transcription initiation. Resulting data represents the consequence of transcriptional regulation in each analyzed state of mammalian cells. Non-overlapping peaks over the CAGE profiles, approximately 200,000 and 150,000 peaks for the human and mouse genomes, were identified and annotated to provide precise location of known promoters as well as novel ones, and to quantify their activities.
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| 7. |
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| 8. |
- Kishida, T., et al.
(författare)
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High-spin isomeric beam line
- 2002
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Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier. - 0168-9002 .- 1872-9576. ; 484:03-jan, s. 45-55
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Tidskriftsartikel (refereegranskat)abstract
- A high-spin isomeric beam line has been constructed at RIKEN based on the inverse kinematics of fusion-evaporation reactions. The beam line provides high-spin isomers as secondary beams, whose intensity is more than 10(5) sec(-1). The characteristics and the present status of the beam line are described.
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| 9. |
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| 10. |
- Gono, Y., et al.
(författare)
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Systematics of high-spin isomers in N=83 isotones and a high-spin isomer beam
- 2002
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Ingår i: European Physical Journal A. - 1434-6001 .- 1434-601X. ; 13:02-jan, s. 5-8
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Tidskriftsartikel (refereegranskat)abstract
- Isomers in N = 83 isotones of Z = 60 66 were studied systematically. Their spins and parities arc,49/2(+) and 27(+) for odd and odd-odd nuclei, respectively. Nearly constant excitation energies of these isomers indicated a decrease of a Z = 64 shell gap energy as Z decreases from 64 to 60 within the framework of a deformed independent-particle model (DIPM). Their configurations are [v(f(tau/2)h(9/2)i(13/2)), pi(h(11/2))(2)](49/2+) and [v(f(7/2)h(9/2)i(13/2)), pi(h(11/2))(2)(d(5/2))(-1)](27+) for odd and odd-odd nuclei, respectively. The shape of the yrast status changes suddenly at spin 49/2(odd) and 27(odd-odd) from a near spherical to an oblate shape. Transitions from isomers are highly hindered because of the shape changes. They may be categorized to be shape isomers. The development of a secondary beam produced by using these high-spin isomers is also described.
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| 11. |
- KOMATSUBARA, T, et al.
(författare)
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HIGH-SPIN STATES IN ODD-ODD NUCLEI
- 1993
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Konferensbidrag (refereegranskat)abstract
- High-spin states in doubly odd nuclei of 124Cs, 126Cs and 124La have been investigated by gamma ray spectroscopy. Rotational bands of pih11/2 x nuh11/2 configuration have been assigned by the blocking argument on the first band crossing frequencies for neighboring odd-A nuclei. In cesium isotopes, the signature inversion of quasiparticle routhians has been observed. The spin of the band head in 124Cs has been determined to be (7+) by means of spectroscopic method. This spin assignment implies that the signature inversion occurs at low spin. The signature dependence becomes normal at higher spins than 17hBAR. The occurrence of the signature inversion in the A approximately 130 mass region is discussed by comparing excitation energies, transition intensities and the shell-model orbits of valence nucleons with those of rare-earth nuclei.
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| 12. |
- Tamagawa, T., et al.
(författare)
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Correlation between musculoskeletal structure of the hand and primate locomotion: Morphometric and mechanical analysis in prehension using the cross- and triple-ratios
- 2020
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 15:5
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Tidskriftsartikel (refereegranskat)abstract
- Biometric ratios of the relative length of the rays in the hand have been analyzed between primate species in the light of their hand function or phylogeny. However, how relative lengths among phalanges are mechanically linked to the grasping function of primates with different locomotor behaviors remains unclear. To clarify this, we calculated cross and triple-ratios, which are related to the torque distribution, and the torque generation mode at different joint angles using the lengths of the phalanges and metacarpal bones in 52 primates belonging to 25 species. The torque exerted on the finger joint and traction force of the flexor tendons necessary for a cylindrical grip and a suspensory hand posture were calculated using the moment arm of flexor tendons measured on magnetic resonance images, and were compared among Hylobates spp., Ateles sp., and Papio hamadryas. Finally, the torques calculated from the model were validated by a mechanical study detecting the force exerted on the phalanx by pulling the digital flexor muscles during suspension in these three species. Canonical discriminant analysis of cross and triple-ratios classified primates almost in accordance with their current classification based on locomotor behavior. The traction force was markedly reduced with flexion of the MCP joint parallel to the torque in brachiating primates; this was notably lower in the terrestrial quadrupedal primates than in the arboreal primates at mild flexion. Our mechanical study supported these features in the torque and traction force generation efficiencies. Our results suggest that suspensory or terrestrial quadrupedal primates have hand structures that can exert more torque at a suspensory posture, or palmigrade and digitigrade locomotion, respectively. Furthermore, our study suggests availability of the cross and triple-ratios as one of the indicators to estimate the hand function from the skeletal structure.
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| 13. |
- Papadopoulos, N G, et al.
(författare)
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International consensus on (ICON) pediatric asthma.
- 2012
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Ingår i: Allergy. - : Wiley. - 1398-9995 .- 0105-4538. ; 67:8, s. 976-97
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Tidskriftsartikel (refereegranskat)abstract
- Asthma is the most common chronic lower respiratory disease in childhood throughout the world. Several guidelines and/or consensus documents are available to support medical decisions on pediatric asthma. Although there is no doubt that the use of common systematic approaches for management can considerably improve outcomes, dissemination and implementation of these are still major challenges. Consequently, the International Collaboration in Asthma, Allergy and Immunology (iCAALL), recently formed by the EAACI, AAAAI, ACAAI, and WAO, has decided to propose an International Consensus on (ICON) Pediatric Asthma. The purpose of this document is to highlight the key messages that are common to many of the existing guidelines, while critically reviewing and commenting on any differences, thus providing a concise reference. The principles of pediatric asthma management are generally accepted. Overall, the treatment goal is disease control. To achieve this, patients and their parents should be educated to optimally manage the disease, in collaboration with healthcare professionals. Identification and avoidance of triggers is also of significant importance. Assessment and monitoring should be performed regularly to re-evaluate and fine-tune treatment. Pharmacotherapy is the cornerstone of treatment. The optimal use of medication can, in most cases, help patients control symptoms and reduce the risk for future morbidity. The management of exacerbations is a major consideration, independent of chronic treatment. There is a trend toward considering phenotype-specific treatment choices; however, this goal has not yet been achieved.
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| 14. |
- Pennells, Lisa, et al.
(författare)
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Equalization of four cardiovascular risk algorithms after systematic recalibration : individual-participant meta-analysis of 86 prospective studies
- 2019
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 40:7, s. 621-
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Tidskriftsartikel (refereegranskat)abstract
- Aims: There is debate about the optimum algorithm for cardiovascular disease (CVD) risk estimation. We conducted head-to-head comparisons of four algorithms recommended by primary prevention guidelines, before and after ‘recalibration’, a method that adapts risk algorithms to take account of differences in the risk characteristics of the populations being studied.Methods and results: Using individual-participant data on 360 737 participants without CVD at baseline in 86 prospective studies from 22 countries, we compared the Framingham risk score (FRS), Systematic COronary Risk Evaluation (SCORE), pooled cohort equations (PCE), and Reynolds risk score (RRS). We calculated measures of risk discrimination and calibration, and modelled clinical implications of initiating statin therapy in people judged to be at ‘high’ 10 year CVD risk. Original risk algorithms were recalibrated using the risk factor profile and CVD incidence of target populations. The four algorithms had similar risk discrimination. Before recalibration, FRS, SCORE, and PCE over-predicted CVD risk on average by 10%, 52%, and 41%, respectively, whereas RRS under-predicted by 10%. Original versions of algorithms classified 29–39% of individuals aged ≥40 years as high risk. By contrast, recalibration reduced this proportion to 22–24% for every algorithm. We estimated that to prevent one CVD event, it would be necessary to initiate statin therapy in 44–51 such individuals using original algorithms, in contrast to 37–39 individuals with recalibrated algorithms.Conclusion: Before recalibration, the clinical performance of four widely used CVD risk algorithms varied substantially. By contrast, simple recalibration nearly equalized their performance and improved modelled targeting of preventive action to clinical need.
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| 15. |
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| 16. |
- Wang, S. Y., et al.
(författare)
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Band structures in I-123
- 2006
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Ingår i: Journal of Physics G. - : IOP Publishing. - 0954-3899 .- 1361-6471. ; 32:3, s. 283-294
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Tidskriftsartikel (refereegranskat)abstract
- Excited states of I-123 were populated via the Cd-116(N-14, alpha 3n) reaction at 65 MeV. The resultant gamma-rays were detected using standard gamma-ray spectroscopic techniques with the NORDBALL detector array. Two previously known positive-parity Delta I = 2 sequences have been extended up to 31/2(+) and 41/2(+). In addition, a number of Delta I = 1 transitions linking the two Delta I = 2 sequences have been observed. It is suggested that both Delta I = 2 sequences are based on a common configuration. This Delta I = 1 band is proposed to be built predominantly on the 97/2[404]7/2(+) oblate configuration, based on the energylevel spectra, B(MI)/B(E2) ratios and the theoretical predictions from the particle-rotor model. The previously identified Delta I = 1 rotational band built on the prolate g(9/2)[404]9/2(+) orbital has also been extended to higher spins. Another previously identified but weakly populated Delta I = 1 band is confirmed and is proposed to be built on the d(5/2)[413]5/2' configuration with the ground state of I-123 as the bandhead.
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| 17. |
- Wang, S. Y., et al.
(författare)
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High-spin level scheme of Cs-126
- 2004
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Ingår i: Gaoneng wuli yu he wuli. - 0254-3052. ; 28:5, s. 491-494
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Tidskriftsartikel (refereegranskat)abstract
- High-spin states of Cs-126 have been populated via the Cd-116(N-14, 4n) Cs-126 reaction. The experiment was performed at Niels Bohr Institute in Denmark in 1991. After careful data analysis, most of the previously-known bands have been pushed up to much higher spins and 3 new rotational sequences have been identified. Spin, parity and configuration assignments are tentatively proposed for all of the observed bands.
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| 18. |
- Wang, S. Y., et al.
(författare)
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Structure of the pi g(7/2) 404 7/2(+) band in odd proton nucleus I-123
- 2004
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Ingår i: Chinese Physics Letters. - 0256-307X .- 1741-3540. ; 21:6, s. 1024-1026
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Tidskriftsartikel (refereegranskat)abstract
- High spin states of the odd proton nucleus I-123 have been populated in the reaction Cd-116(N-14, 5n2p) at a beam energy of 65 MeV. Two previously known positive-parity DeltaI = 2 sequences have been extended up to 31/2(+) and 41/2(+). In addition, a number of DeltaI = 1 transitions linking the two DeltaI = 2 sequences have been observed. It is suggested that both the DeltaI = 2 sequences are built upon the oblate pi(g) (7/2)[404]7/2(+) Nilsson configuration.
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| 19. |
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| 20. |
- Hosaka, K, et al.
(författare)
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Therapeutic paradigm of dual targeting VEGF and PDGF for effectively treating FGF-2 off-target tumors
- 2020
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1, s. 3704-
-
Tidskriftsartikel (refereegranskat)abstract
- FGF-2 displays multifarious functions in regulation of angiogenesis and vascular remodeling. However, effective drugs for treating FGF-2+ tumors are unavailable. Here we show that FGF-2 modulates tumor vessels by recruiting NG2+ pricytes onto tumor microvessels through a PDGFRβ-dependent mechanism. FGF-2+ tumors are intrinsically resistant to clinically available drugs targeting VEGF and PDGF. Surprisingly, dual targeting the VEGF and PDGF signaling produces a superior antitumor effect in FGF-2+ breast cancer and fibrosarcoma models. Mechanistically, inhibition of PDGFRβ ablates FGF-2-recruited perivascular coverage, exposing anti-VEGF agents to inhibit vascular sprouting. These findings show that the off-target FGF-2 is a resistant biomarker for anti-VEGF and anti-PDGF monotherapy, but a highly beneficial marker for combination therapy. Our data shed light on mechanistic interactions between various angiogenic and remodeling factors in tumor neovascularization. Optimization of antiangiogenic drugs with different principles could produce therapeutic benefits for treating their resistant off-target cancers.
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| 21. |
- Konishi, T, et al.
(författare)
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Electronic structure of the strongly hybridized ferromagnet CeFe2
- 2000
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Ingår i: PHYSICAL REVIEW B. - : AMERICAN PHYSICAL SOC. - 0163-1829. ; 62:21, s. 14304-14312
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Tidskriftsartikel (refereegranskat)abstract
- We report on results from high-energy spectroscopic measurements on CeFe2, a system of particular interest due to its anomalous ferromagnetism with an unusually low Curie temperature and small magnetization compared to the other rare-earth iron Laves phas
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| 22. |
- Konishi, T, et al.
(författare)
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Photoemission and inverse-photoemission study of ferromagnetic valence fluctuating system CeFe2
- 1998
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Ingår i: JOURNAL OF ELECTRON SPECTROSCOPY AND RELATED PHENOMENA. - : ELSEVIER SCIENCE BV. - 0368-2048. ; 88, s. 303-307
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Various electron-spectroscopic results including core-level X-ray photoemission, X-ray absorption, Ce 3d-4f and 4d-4f resonant photoemission, and inverse-photoemission spectroscopy on the valence fluctuating ferromagnet CeFe2 are presented and analyzed wi
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| 23. |
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| 24. |
- SUGAWARA, M, et al.
(författare)
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HIGH-SPIN STATES IN RB-79
- 1995
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Ingår i: JOURNAL OF THE PHYSICAL SOCIETY OF JAPAN. - : PHYSICAL SOCIETY JAPAN KIKAI-SHINKO BUILDING. ; 64:1
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Annan publikation (övrigt vetenskapligt/konstnärligt)
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| 25. |
- Fernandes, SJ, et al.
(författare)
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Non-parametric combination analysis of multiple data types enables detection of novel regulatory mechanisms in T cells of multiple sclerosis patients
- 2019
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1, s. 11996-
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Tidskriftsartikel (refereegranskat)abstract
- Multiple Sclerosis (MS) is an autoimmune disease of the central nervous system with prominent neurodegenerative components. The triggering and progression of MS is associated with transcriptional and epigenetic alterations in several tissues, including peripheral blood. The combined influence of transcriptional and epigenetic changes associated with MS has not been assessed in the same individuals. Here we generated paired transcriptomic (RNA-seq) and DNA methylation (Illumina 450 K array) profiles of CD4+ and CD8+ T cells (CD4, CD8), using clinically accessible blood from healthy donors and MS patients in the initial relapsing-remitting and subsequent secondary-progressive stage. By integrating the output of a differential expression test with a permutation-based non-parametric combination methodology, we identified 149 differentially expressed (DE) genes in both CD4 and CD8 cells collected from MS patients. Moreover, by leveraging the methylation-dependent regulation of gene expression, we identified the gene SH3YL1, which displayed significant correlated expression and methylation changes in MS patients. Importantly, silencing of SH3YL1 in primary human CD4 cells demonstrated its influence on T cell activation. Collectively, our strategy based on paired sampling of several cell-types provides a novel approach to increase sensitivity for identifying shared mechanisms altered in CD4 and CD8 cells of relevance in MS in small sized clinical materials.
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| 26. |
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| 27. |
- Morikawa, H, et al.
(författare)
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Differential roles of epigenetic changes and Foxp3 expression in regulatory T cell-specific transcriptional regulation
- 2014
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 111:14, s. 5289-5294
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Tidskriftsartikel (refereegranskat)abstract
- Naturally occurring regulatory T (Treg) cells, which specifically express the transcription factor forkhead box P3 (Foxp3), are engaged in the maintenance of immunological self-tolerance and homeostasis. By transcriptional start site cluster analysis, we assessed here how genome-wide patterns of DNA methylation or Foxp3 binding sites were associated with Treg-specific gene expression. We found that Treg-specific DNA hypomethylated regions were closely associated with Treg up-regulated transcriptional start site clusters, whereas Foxp3 binding regions had no significant correlation with either up- or down-regulated clusters in nonactivated Treg cells. However, in activated Treg cells, Foxp3 binding regions showed a strong correlation with down-regulated clusters. In accordance with these findings, the above two features of activation-dependent gene regulation in Treg cells tend to occur at different locations in the genome. The results collectively indicate that Treg-specific DNA hypomethylation is instrumental in gene up-regulation in steady state Treg cells, whereas Foxp3 down-regulates the expression of its target genes in activated Treg cells. Thus, the two events seem to play distinct but complementary roles in Treg-specific gene expression.
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| 28. |
- Sakurai, T., et al.
(författare)
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RNA-binding motif protein 47 inhibits Nrf2 activity to suppress tumor growth in lung adenocarcinoma
- 2016
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Ingår i: Oncogene. - : Springer Science and Business Media LLC. - 0950-9232 .- 1476-5594. ; 35:38, s. 5000-5009
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Tidskriftsartikel (refereegranskat)abstract
- RNA-binding proteins provide a new layer of posttranscriptional regulation of RNA during cancer progression. We identified RNA-binding motif protein 47 (RBM47) as a target gene of transforming growth factor (TGF)-beta in mammary gland epithelial cells (NMuMG cells) that have undergone the epithelial-to-mesenchymal transition. TGF-beta repressed RBM47 expression in NMuMG cells and lung cancer cell lines. Expression of RBM47 correlated with good prognosis in patients with lung, breast and gastric cancer. RBM47 suppressed the expression of cell metabolism-related genes, which were the direct targets of nuclear factor erythroid 2-related factor 2 (Nrf2; also known as NFE2L2). RBM47 bound to KEAP1 and Cullin 3 mRNAs, and knockdown of RBM47 inhibited their protein expression, which led to enhanced binding of Nrf2 to target genomic regions. Knockdown of RBM47 also enhanced the expression of some Nrf2 activators, p21/CDKN1A and MafK induced by TGF-beta. Both mitochondrial respiration rates and the side population cells in lung cancer cells increased in the absence of RBM47. Our findings, together with the enhanced tumor formation and metastasis of xenografted mice by knockdown of the RBM47 expression, suggested tumor-suppressive roles for RBM47 through the inhibition of Nrf2 activity.
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| 29. |
- Tsuji, M., et al.
(författare)
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Foxc2 influences alveolar epithelial cell differentiation during lung development
- 2017
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Ingår i: Development Growth & Differentiation. - : Wiley. - 0012-1592. ; 59:6, s. 501-514
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Tidskriftsartikel (refereegranskat)abstract
- FOXC2, a forkhead transcriptional factor, is a candidate gene for congenital heart diseases and lymphedema-distichiasis syndrome and yellow nail syndrome; however, there are no reports on Foxc2 and the development of the lung. We have identified lung abnormalities in Foxc2-knockout embryos during investigation of cardiac development. The aim of this study was to clarify the morphological characteristics during lung development using ICR-Foxc2 knockout lungs. Mutant fetuses at embryonic days 10.5-18.5 were obtained from mating of Foxc2(+/-) mice and then analyzed. Notably, Foxc2-knockout lungs appeared parenchymatous and much smaller than those of the wild-type littermates. In the Foxc2 knockout lungs, the capillary beds remained distant from the alveolar epithelium until the late stages, the number of type2 alveolar cells per alveolar progenitor cell was lower and the type1 alveolar cells were thicker in Foxc2 knockout mice. In contrast, Foxc2 expression was only detected in the mesenchyme of the lung buds at E10.5, and it disappeared at E11.5 in Foxc2-LacZ knockin mice. Furthermore, the expression of Lef1 was significantly inhibited in E11.5 lungs. All of these results suggest that the abnormalities in Foxc2 knockout mice may involve maldifferentiation of alveolar epithelial cells and capillary vessel endothelial-alveolar epithelial approach as well as lymph vessel malformation. This is the first report about relationship between Foxc2 and lung development. This animal model might provide an important clue for elucidating the mechanism of lung development and the cause of respiratory diseases.
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