Researchers from Texas described a novel mechanism involving caveolin-1-derived 7-mer peptide (CSP7) that attenuates scarring that developed in the lungs and published their results in Scientific Reports. CSP7 could therefore be a potential treatment for diseases like idiopathic pulmonary fibrosis (IPF), which are characterized by lung scarring.

The exact cause of IPF is still not known. However, it is known that the disease is associated with the dysregulation of autophagy in alveolar-epithelial cells and the interaction between apoptotic-alveolar-epithelial cells and proliferative-myofibroblasts. 

Previous research has shown that CSP7 can attenuate the effect of lung fibrosis by improving the viability of alveolar-epithelial cells. Here, a team of researchers from the Texas Lung Injury Institute led by Sreerama Shetty, PhD, assessed whether and how CSP7 regulates autophagy in fibrotic-lung alveolar-epithelial cells.


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Using a mouse model of pulmonary fibrosis, the team found that p53 and autophagic proteins were markedly upregulated in the alveolar epithelial cells of the animals. 

Read more about the etiology of IPF

The researchers found that CSP7 treatment not only abolished the upregulation of p53 and autophagic proteins in these animals, it also revoked their upregulation. Further experiments showed that CSP7 blocks the interaction of caveolin-1 with the autophagic proteins LC3B2 and p62 in alveolar-epithelial cells. 

Finally, mice that were missing p53 in their alveolar-epithelial cells did not respond to changes in autophagy proteins caused by silica or bleomycin, which are normally used to induce scarring in the lungs of the animals to serve as models of pulmonary fibrosis. These mice did also not respond to treatment with CSP7 treatment confirming that CSP7 acts through p53.

“Our study identifies CSP7 as a promising candidate for the treatment of dysregulated autophagy reported in various diseases including IPF,” the researchers concluded.

Reference

Venkatesan S, Fan L, Tang H, Konduru NV, Shetty S. Caveolin-1 scaffolding domain peptide abrogates autophagy dysregulation in pulmonary fibrosis. Sci Rep. 2022;12(1):11086. doi:10.1038/s41598-022-14832-4