The important role of Cav1 in inducing peritoneal membrane epithelial-mesenchymal transition and fibrosis

 

Peritoneal dialysis (PD) is a replacement therapy for patients with severe rental disease. However, the repeat of the treatment alters dialytic function of peritoneal membrane and leads to PD discontinuation, due to increased epithelial-mesenchymal transition (EMT), thickness, and fibrosis of peritoneum. Strippoli et al. found Caveolin-1 (Cav1) acts as a critical factor in this process. The article was published in EMBO Molecular Medicine, recently.

 

The absence of Cav1 leads to a loss of caveolae in mice, which related to aberrant lipid metabolism, pulmonary and cardiac abnormalities. In this study, researchers found Cav1^-/- mice had an increased EMT, thickness, and fibrosis in their peritoneal membrane, moreover, exposure of those mice to PD fluids aggravated the phenotype and increased the number of FSP-1/cytokeratin-positive cells that invade the sub-mesothelial stroma. The absence of Cav1 results in a hyperactivation of MEK-ERK1/2-Snail-1 pathway and induces mesenchymal-like features of endothelial cells (EC). The inhibition of MEK-ERK1/2-Snail-1 pathway attenuated EMT fibrosis in both Cav1^-/- and wild-type mice. The findings demonstrate that Cav1 acts as an important regulator in promoting EMT and fibrosis of peritoneum, and addressed that the inhibition of MEK-ERK1/2-Snail-1 pathway may be a potential therapeutic strategy for treating the malfunction of peritoneal membrane.

 

Reference:
EMBO Mol Med. 2014 Dec 30;7(1):102-23.

Related Products

Cat.No.	Product Name	Information
S1020	PD184352 (CI-1040)	PD184352 (CI-1040) is an ATP non-competitive MEK1/2 inhibitor with IC50 of 17 nM in cell-based assays, 100-fold more selective for MEK1/2 than MEK5. PD184352 (CI-1040) selectively induces apoptosis.

Related Targets

MEK