| 1. |
- Bagher, Mariam, et al.
(författare)
-
Crosstalk between mast cells and lung fibroblasts is modified by alveolar extracellular matrix and influences epithelial migration
- 2021
-
Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1661-6596 .- 1422-0067. ; 22:2
-
Tidskriftsartikel (refereegranskat)abstract
- Mast cells play an important role in asthma, however, the interactions between mast cells, fibroblasts and epithelial cells in idiopathic pulmonary fibrosis (IPF) are less known. The objectives were to investigate the effect of mast cells on fibroblast activity and migration of epithelial cells. Lung fibroblasts from IPF patients and healthy individuals were co-cultured with LAD2 mast cells or stimulated with the proteases tryptase and chymase. Human lung fibroblasts and mast cells were cultured on cell culture plastic plates or decellularized human lung tissue (scaffolds) to create a more physiological milieu by providing an alveolar extracellular matrix. Released mediators were analyzed and evaluated for effects on epithelial cell migration. Tryptase increased vascular endothelial growth factor (VEGF) release from fibroblasts, whereas co-culture with mast cells increased IL-6 and hepatocyte growth factor (HGF). Culture in scaffolds increased the release of VEGF compared to culture on plastic. Migration of epithelial cells was reduced by IL-6, while HGF and conditioned media from scaffold cultures promoted migration. In conclusion, mast cells and tryptase increased fibroblast release of mediators that influenced epithelial migration. These data indicate a role of mast cells and tryptase in the interplay between fibroblasts, epithelial cells and the alveolar extracellular matrix in health and lung disease.
|
|
| 2. |
- Löfdahl, Anna, et al.
(författare)
-
Pulmonary 5-HT 2B receptor expression in fibrotic interstitial lung diseases.
- 2023
-
Ingår i: Acta Histochemica. - : Elsevier BV. - 0065-1281. ; 125:3, s. 1-8
-
Tidskriftsartikel (refereegranskat)abstract
- Pulmonary fibrosis is a severe condition in interstitial lung diseases (ILD) such as idiopathic pulmonary fibrosis (IPF) and systemic sclerosis-ILD, where the underlying mechanism is not well defined and with no curative treatments available. Serotonin (5-HT) signaling via the 5-HT 2B receptor has been recognized as a promising preclinical target for fibrosis. Despite this, the involvement of the 5-HT 2B receptor in fibrotic ILD is widely unexplored. This work highlights the spatial pulmonary distribution of the 5-HT 2B receptor in patients with IPF and systemic sclerosis-ILD. We show that the 5-HT 2B receptor is located in typical pathological structures e.g. honeycomb cysts and weakly in fibroblast foci. Together with immunohistochemistry and immunofluorescence stainings of patient derived distal lung tissues, we identified cell targets for 5-HT 2B receptor interference in type II alveolar epithelial cells, endothelial cells and M2 macrophages. Our results emphasize the role of 5-HT 2B receptor as a target in lung fibrosis, warranting further consideration in targeting fibrotic ILDs.
|
|
| 3. |
- Müller, Catharina, et al.
(författare)
-
Protein signatures of remodeled airways in transplanted lungs with Bronchiolitis Obliterans Syndrome obtained using laser capture microdissection
- 2021
-
Ingår i: American Journal of Pathology. - : Elsevier BV. - 1525-2191 .- 0002-9440. ; 191:8, s. 1398-1411
-
Tidskriftsartikel (refereegranskat)abstract
- Bronchiolitis obliterans syndrome (BOS), a common form of chronic lung allograft dysfunction, is the major limitation to long-term survival after lung transplantation. The histological correlate is progressive, fibrotic occlusion of small airways, obliterative bronchiolitis lesions, ultimately leading to organ failure. The molecular composition of these lesions is unknown. By laser-capture microdissection and optimized sample preparation protocols for mass spectrometry the protein composition of the lesions in explanted lungs from four end-stage BOS patients were analysed. Immunohistochemistry and immunofluorescence were used to determine the spatial distribution of commonly identified proteins on the tissue level, protein signatures for in total 14 OB-lesions were established. A set of 39 proteins identified in more than 75% of lesions included distinct structural proteins (collagen type IV and VI) and cellular components (actins, vimentin, tryptase). Each respective lesion exhibited a unique composition of proteins (on average n=66 proteins), thereby mirroring the morphological variation of the lesions. Antibody-based staining confirmed these MS-based findings. The 14 analyzed OB-lesions showed variations in their protein content, but also common features. This study provides molecular and morphological insights into the development of chronic rejection after lung transplantation. The protein patterns in the lesions were correlated to pathways of extracellular matrix organization, tissue development and wound healing processes.
|
|
| 4. |
- Westergren-Thorsson, Gunilla, et al.
(författare)
-
Increased deposition of glycosaminoglycans and altered structure of heparan sulfate in idiopathic pulmonary fibrosis
- 2017
-
Ingår i: International Journal of Biochemistry & Cell Biology. - : Elsevier BV. - 1357-2725 .- 1878-5875. ; 83, s. 27-38
-
Tidskriftsartikel (refereegranskat)abstract
- Idiopathic pulmonary fibrosis (IPF) is characterized by aberrant deposition of extracellular matrix (ECM) constituents, including glycosaminoglycans (GAGs), that may play a role in remodelling processes by influencing critical mediators such as growth factors. We hypothesize that GAGs may be altered in IPF and that this contribute to create a pro-fibrotic environment. The aim of this study was therefore to examine the fine structure of heparan sulfate (HS), chondroitin/dermatan sulfate (CS/DS) and hyaluronan (HA) in lung samples from IPF patients and from control subjects. GAGs in lung samples from severe IPF patients and donor lungs were analyzed with HPLC. HS was assessed by immunohistochemistry and collagen was quantified as hydroxyproline content. The total amount of HS, CS/DS and HA was increased in IPF lungs but there was no significant difference in the total collagen content. We found a relative increase in total sulfation of HS due to increment of 2-O, 6-O and N-sulfation and a higher proportion of sulfation in CS/DS. Highly sulfated HS was located in the border zone between denser areas and more normal looking alveolar parenchyma in basement membranes of blood vessels and airways, that were immuno-positive for perlecan, as well as on the cell surface of spindle-shaped cells in the alveolar interstitium. These findings show for the first time that both the amount and structure of glycosaminoglycans are altered in IPF. These changes may contribute to the tissue remodelling in IPF by altering growth factor retention and activity, creating a pro-fibrotic ECM landscape. (C) 2016 The Authors. Published by Elsevier Ltd.
|
|
| 5. |
- Wijk, Sofia C., et al.
(författare)
-
Ciliated (FOXJ1+) Cells Display Reduced Ferritin Light Chain in the Airways of Idiopathic Pulmonary Fibrosis Patients
- 2022
-
Ingår i: Cells. - : MDPI AG. - 2073-4409. ; 11:6
-
Tidskriftsartikel (refereegranskat)abstract
- Cell-based therapies hold great promise in re-establishing organ function for many diseases, including untreatable lung diseases such as idiopathic pulmonary fibrosis (IPF). However, many hurdles still remain, in part due to our lack of knowledge about the disease-driving mechanisms that may affect the cellular niche and thereby possibly hinder the function of any transplanted cells by imposing the disease phenotype onto the newly generated progeny. Recent findings have demonstrated increased ciliation of lung cells from IPF patients, but how this affects ciliated cell function and the airway milieu is not well-known. Here, we performed single-cell RNA sequencing on primary ciliated (FOJ1+) cells isolated from IPF patients and from healthy control donors. The sequencing identified multiple biological processes, such as cilium morphogenesis and cell signaling, that were significantly changed between IPF and healthy ciliated cells. Ferritin light chain (FTL) was downregulated in IPF, which suggests that iron metabolism may be affected in the IPF ciliated cells. The RNA expression was confirmed at the protein level with histological localization in lung tissue, prompting future functional assays to reveal the potential role of FTL. Taken together, our data demonstrate the importance of careful analyses in pure cell populations to better understand the IPF disease mechanism.
|
|
