Functional molecules in mesothelial-to-mesenchymal transition revealed by transcriptome analyses

The Journal of Pathology
Sara NamvarSarah E Herrick

Abstract

Peritoneal fibrosis is a common complication of abdominal and pelvic surgery, and can also be triggered by peritoneal dialysis, resulting in treatment failure. In these settings, fibrosis is driven by activated myofibroblasts that are considered to be partly derived by mesothelial-to-mesenchymal transition (MMT). We hypothesized that, if the molecular signature of MMT could be better defined, these insights could be exploited to block this pathological cellular transition. Rat peritoneal mesothelial cells were purified by the use of an antibody against HBME1, a protein present on mesothelial cell microvilli, and streptavidin nanobead technology. After exposure of sorted cells to a well-known mediator of MMT, transforming growth factor (TGF)-β1, RNA sequencing was undertaken to define the transcriptomes of mesothelial cells before and during early-phase MMT. MMT was associated with dysregulation of transcripts encoding molecules involved in insulin-like growth factor (IGF) and bone morphogenetic protein (BMP) signalling. The application of either recombinant BMP4 or IGF-binding protein 4 (IGFBP4) ameliorated TGF-β1-induced MMT in culture, as judged from the retention of epithelial morphological and molecular phenotypes, and redu...Continue Reading

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Citations

Aug 11, 2019·The Journal of Pathology·Filipa M LopesAdrian S Woolf
Jul 30, 2020·American Journal of Physiology. Lung Cellular and Molecular Physiology·Nathanael PruettChuong D Hoang
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Dec 14, 2021·Frontiers in Molecular Biosciences·Giulia MatusaliRaffaele Strippoli

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Methods Mentioned

BETA
FACS
Fluorescence microscopy

Software Mentioned

GraphPad
GraphPad Prism
Pro Plus
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