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Sci Rep ; 14(1): 12744, 2024 06 03.
Article in English | MEDLINE | ID: mdl-38830931

ABSTRACT

Transforming growth factor ß (TGF-ß) is implicated in both mesothelial-to-mesenchymal transition (MMT) and cellular senescence of human peritoneal mesothelial cells (HPMCs). We previously showed that senescent HPMCs could spontaneously acquire some phenotypic features of MMT, which in young HPMCs were induced by TGF-ß. Here, we used electron microscopy, as well as global gene and protein profiling to assess in detail how exposure to TGF-ß impacts on young and senescent HPMCs in vitro. We found that TGF-ß induced structural changes consistent with MMT in young, but not in senescent HPMCs. Of all genes and proteins identified reliably in HPMCs across all treatments and states, 4,656 targets represented overlapping genes and proteins. Following exposure to TGF-ß, 137 proteins and 46 transcripts were significantly changed in young cells, compared to 225 proteins and only 2 transcripts in senescent cells. Identified differences between young and senescent HPMCs were related predominantly to wound healing, integrin-mediated signalling, production of proteases and extracellular matrix components, and cytoskeleton structure. Thus, the response of senescent HPMCs to TGF-ß differs or is less pronounced compared to young cells. As a result, the character and magnitude of the postulated contribution of HPMCs to TGF-ß-induced peritoneal remodelling may change with cell senescence.


Subject(s)
Cellular Senescence , Epithelial Cells , Peritoneum , Transforming Growth Factor beta , Humans , Cellular Senescence/drug effects , Transforming Growth Factor beta/metabolism , Transforming Growth Factor beta/pharmacology , Epithelial Cells/metabolism , Epithelial Cells/drug effects , Peritoneum/cytology , Peritoneum/metabolism , Epithelial-Mesenchymal Transition/drug effects , Cells, Cultured , Epithelium/metabolism , Epithelium/drug effects , Signal Transduction/drug effects , Gene Expression Profiling
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