| 1. |
- Patrakka, Jaakko, et al.
(författare)
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Expression and subcellular distribution of novel glomerulus-associated proteins dendrin, ehd3, sh2d4a, plekhh2, and 2310066E14Rik
- 2007
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Ingår i: Journal of the American Society of Nephrology. - : Ovid Technologies (Wolters Kluwer Health). - 1046-6673 .- 1533-3450. ; 18:3, s. 689-697
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Tidskriftsartikel (refereegranskat)abstract
- The glomerular capillary tuft is a highly specialized microcapillary that is dedicated to function as a sophisticated molecular sieve. The glomerulus filter has a unique molecular composition, and several essential glomerular proteins are expressed in the kidney exclusively by glomerular podocytes. A catalog of > 300 glomerulus-upregulated transcripts that were identified using expressed sequence tag profiling and microarray analysis was published recently. This study characterized the expression profile of five glomerulus-upregulated transcripts/proteins (ehd3, dendrin, sh2d4a, plekhh2, and 2310066E14Rik) in detail. The expression pattern of these novel glomerular transcripts in various mouse tissues was studied using reverse transcriptase-PCR, Northern blotting, and in situ hybridization. For studying the distribution of corresponding proteins, polyclonal antibodies were raised against the gene products, and Western blotting, immunofluorescence, and immunoelectron microscopic analyses were performed. Remarkably, it was discovered that all five transcripts/proteins were expressed in the kidney exclusively by glomerular cells. Ehd3 was expressed only by glomerular endothelial cells. Importantly, ehd3 is the first gene ever shown to be expressed exclusively by glomerular endothelial cells and not by other endothelial cells in the kidney. Dendrin, sh2d4a, plekhh2, and 2310066E14Rik, however, were transcribed solely by podocytes. With the use of polyclonal antibodies, dendrin, sh2d4a, and plekhh2 proteins were localized to the slit diaphragm and the foot process, whereas 2310066E14Rik protein was localized to the podocyte major processes and cell body. This study provides fresh insights into glomerular biology and uncovers new possibilities to explore the role of these novel proteins in the glomerular physiology and pathology.
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| 2. |
- Takemoto, Minoru, et al.
(författare)
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Large-scale identification of genes implicated in kidney glomerulus development and function.
- 2006
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Ingår i: The EMBO journal. - : Wiley. - 0261-4189 .- 1460-2075. ; 25:5, s. 1160-74
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Tidskriftsartikel (refereegranskat)abstract
- To advance our understanding of development, function and diseases in the kidney glomerulus, we have established and large-scale sequenced cDNA libraries from mouse glomeruli at different stages of development, resulting in a catalogue of 6053 different genes. The glomerular cDNA clones were arrayed and hybridized against a series of labeled targets from isolated glomeruli, non-glomerular kidney tissue, FACS-sorted podocytes and brain capillaries, which identified over 300 glomerular cell-enriched transcripts, some of which were further sublocalized to podocytes, mesangial cells and juxtaglomerular cells by in situ hybridization. For the earliest podocyte marker identified, Foxc2, knockout mice were used to analyze the role of this protein during glomerular development. We show that Foxc2 controls the expression of a distinct set of podocyte genes involved in podocyte differentiation and glomerular basement membrane maturation. The primary podocyte defects also cause abnormal differentiation and organization of the glomerular vascular cells. We surmise that studies on the other novel glomerulus-enriched transcripts identified in this study will provide new insight into glomerular development and pathomechanisms of disease.
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| 3. |
- Xiao, Chao, et al.
(författare)
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RBBP6 increases radioresistance and serves as a therapeutic target for preoperative radiotherapy in colorectal cancer
- 2018
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Ingår i: Cancer Science. - : Blackwell Publishing. - 1347-9032 .- 1349-7006. ; 109:4, s. 1075-1087
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Tidskriftsartikel (refereegranskat)abstract
- Radiotherapy (RT) can be used as preoperative treatment to downstage initially unresectable locally rectal carcinoma, but the radioresistance and recurrence remain significant problems. Retinoblastoma binding protein 6 (RBBP6) has been implicated in the regulation of cell cycle, apoptosis and chemoresistance both in vitro and in vivo. This study investigated whether the inhibition of RBBP6 expression would improve radiosensitivity in human colorectal cancer cells. After SW620 and HT29 cells were exposed to radiation, the levels of RBBP6 mRNA and protein increased over time in both two cells. Moreover, a significant reduction in clonogenic survival and a decrease in cell viability in parallel with an obvious increase in cell apoptosis were demonstrated in irradiated RBBP6-knockdown cells. Besides, transfection with RBBP6 shRNA improved levels of G2-M phase arrest which blocked the cells in a more radiosensitive period of the cell cycle. These observations indicated that cell cycle and apoptosis mechanisms may be connected with tumor cell survival following radiotherapy. In vivo, tumor growth rate of nude mice in RBBP6-knockdown group was significantly slower than that in other groups. These results indicated that RBBP6 overexpression could resist colorectal cancer cells against radiation by regulating cell cycle and apoptosis pathways, and inhibition of RBBP6 could enhance radiosensitivity of human colorectal cancer.
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| 4. |
- Xiao, Zhijie
(författare)
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Identification and characterization of novel glomerulus-associated genes and proteins
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The kidney is responsible for sieving the circulating blood to eliminate water-soluble waste products and potentially toxic substances from the body. The filtration step occurs in specialized filtration units called glomeruli. Some renal diseases are related to specific glomerular defects, but it is highly likely that the present knowledge gained from previous studies only represents a small proportion of genes and proteins that have important roles for normal kidney function. To identify other genes with roles for glomerular filtration function, our group developed GlomBase, which is a glomerular transcript database in which over 300 genes are highly glomerulus specific. Among those genes, several genes with highest glomerular expression were chosen for further analysis, but this thesis is mainly based on studies on three of them, dendrin, adenylate cyclase type I (Adcy1), and Crumbs homolog 2 (Crb2). Dendrin is a cytosolic protein previously identified only in the brain. However, we localized dendrin in the kidney specifically to the glomerular podocytes. Furthermore, we generated a polyclonal antibody against this novel glomerular protein. We detected that the earliest dendrin expression during glomerular maturation is at the capillary loop stage, and that it is located in the cytoplasmic face of the podocyte slit diaphragm. Unexpectedly, inactivation of the dendrin gene in mouse did not generate any obvious phenotype. Dendrin -/- mice were born at an expected Mendelian ratio and macroscopically all organs appeared normal. By the age of 1.2 years, no signs of renal impairment have been observed in the dendrin-/- mice. Under kidney challenging conditions, dendrin -/- mice show no difference when compared with dendrin +/+ mice. Even though dendrin does not seem to be crucial for the integrity of the glomerular filtration barrier, we do find two proteins that interact with dendrin, and their biological role in podocyte is still under investigation. These results are out scope of this thesis. Adcy1 is one out of nine members of the adenylate cyclase protein family which catalyze the formation of the secondary messenger cAMP. cAMP is involved in a wide variety of cellular signaling processes, including regulation of actin cytoskeleton assembly through PKA. Adcy1 has previously been thought to be expressed only by certain neuronal cells in the brain, but we localized Adcy1 expression to the glomerular podocytes as well. During glomerulogenesis, the Adcy1 expression was detected first at the stage when maturing podocytes develop foot processes. To study the role of Adcy1 gene in the kidney in vivo, we analyzed the kidneys of Adcy1-/- mice (mice generatedby other investigators, that without severe phenotype except mild behavioral abnormalities). We found the glomerulogenesis to proceed normally in Adcy1-/- mice, and in mature mouse, no signs of renal impairment was detected. However, challenging of the kidney with albumin overload caused severe albuminuria in Adcy1-/- mice, whereas wild type mice showed only moderate albumin leakage to the urine. Thus, Adcy1 may in fact be a susceptibility gene for proteinuria. Crb2 is yet another novel podocyte specific protein we identified. Its Drosophila homologue Crumbs is an essential component for epithelial cells organizing apicalbasal polarity and adherent junctions. In the mouse, it is expressed only in brain, kidney and heart. In the kidney, it is specifically located in the glomerular podocyte slit diaphragm. Interestingly, inactivation of this gene led to arrest the embryonic development after E7.75 and embryonic lethality, which demonstrates the importance of this gene during early embryonic development. The Crb2-/- embryos show defects in neuroepithelium and epithelial mesenchymal transition (EMT) at the primitive streak. The function of Crb2 protein in the glomerulus will be explored later by my colleagues in studies of conditional knockout mice with podocyte specific inactivation of the Crb2 gene. In summary, the discovery and characterization of novel glomerular genes and proteins presented in this thesis has increased our knowledge of glomerular biology as well as on the role of a glomeral gene in early embryogenesis.
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| 5. |
- Xiao, Zhijie, et al.
(författare)
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Wtip- and Gadd45a-Interacting Protein Dendrin Is Not Crucial for the Development or Maintenance of the Glomerular Filtration Barrier
- 2013
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:12, s. e83133-
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Tidskriftsartikel (refereegranskat)abstract
- Glomerular podocyte cells are critical for the function of the renal ultrafiltration barrier. Especially, the highly specialized cell cell junction of podocytes, the slit diaphragm, has a central role in the filtration barrier. This is highlighted by the fact that mutations in molecular components of the slit diaphragm, inclucling nephrin and Cd2-associated protein (Cd2ap), result in proteinuric diseases in man. Dendrin is a poorly characterized cytosalic component of the slit diaphragm in where it interact h nephrin and Cd2ap. Dendrin is highly specific for the podocyte slit diaphragm, suggesting that it has a dedicated role in glomerular filtration barrier. In this study, we have generated a dendrin knockout mouse line and explored the molecular interactions of dendrin. Dendrin-deficient mice were viable, fertile, and had a normal life span. Morphologically, the glomerulogenesis proceeded normally and adult dendrin-deficient mice showed normal glomerular histology. No significant protainuria was observed. Fallowing glomerular injury, lack of dendrin did not affect the severity of the damage or h recovery process. Yeast two-hybrid screen and co-immunoprecipitation experiments showed that dendrin binds to interacting protein (Wtip) and growth arrest and DNA-damage-inducible 45 alpha (Gadd45a). Wtip and Gadd45a mediate gene transcription in the nucleus, suggesting that dendrin may have similar functions in podacytes In line with this, we observed he relocation of dendrin to nucleus in adriamycin nephropathy model. Our results indicate that dendrin is dispensable forth unction of the normal glomerular filtration barrier and that dendrin interacts with Wtip and Gadd45a.
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| 6. |
- Zhang, Lixiu, et al.
(författare)
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Advances in the Application of Perovskite Materials
- 2023
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Ingår i: NANO-MICRO LETTERS. - : SHANGHAI JIAO TONG UNIV PRESS. - 2311-6706. ; 15:1
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Forskningsöversikt (refereegranskat)abstract
- Nowadays, the soar of photovoltaic performance of perovskite solar cells has set off a fever in the study of metal halide perovskite materials. The excellent optoelectronic properties and defect tolerance feature allow metal halide perovskite to be employed in a wide variety of applications. This article provides a holistic review over the current progress and future prospects of metal halide perovskite materials in representative promising applications, including traditional optoelectronic devices (solar cells, light-emitting diodes, photodetectors, lasers), and cutting-edge technologies in terms of neuromorphic devices (artificial synapses and memristors) and pressure-induced emission. This review highlights the fundamentals, the current progress and the remaining challenges for each application, aiming to provide a comprehensive overview of the development status and a navigation of future research for metal halide perovskite materials and devices.
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