Thy-1^+/- fibroblast subsets in the human peritoneum

Area of Science:

• Nephrology
• Cell Biology
• Histology

Background:

• Peritoneal dialysis (PD) can lead to fibrotic thickening of the peritoneum, impairing dialysis function.
• Fibroblast heterogeneity is recognized, with thymocyte differentiation antigen 1 (Thy-1) identifying distinct functional subsets.

Purpose of the Study:

• To investigate the role of Thy-1 positive (Thy-1+) human peritoneal fibroblasts (HPFB) in peritoneal fibrosis during PD.
• To analyze the profibrotic characteristics of Thy-1+/- HPFB subsets.

Main Methods:

• Isolation and analysis of Thy-1+/- HPFB subsets from healthy individuals and PD patients.
• Assessment of fibroblast proliferation, contractile properties, and expression of α-smooth muscle actin, collagen I, and transforming growth factor-β1.

Main Results:

• In healthy omentum, Thy-1+ HPFB comprised ~45% of the population; they were absent in the parietal peritoneum.
• Cultured omentum-derived Thy-1+ HPFB exhibited increased α-smooth muscle actin, collagen I, TGF-β1, proliferation, and contractility compared to Thy-1- cells.
• In PD patients, Thy-1+ HPFB significantly increased, constituting >70% in the omentum and >95% in the parietal peritoneum.

Conclusions:

• Thy-1+ HPFB represent a distinct, profibrotic fibroblast subset.
• The expansion of Thy-1+ HPFB in PD patients is strongly associated with peritoneal fibrosis.
• Targeting Thy-1+ HPFB expansion may offer a therapeutic strategy to mitigate peritoneal fibrosis in PD.