GEO series

Non-canonical Hedgehog signaling via GLI2 promotes pancreatic stellate cell activation and fibrosis in chronic pancreatitis

GSE281427 Mus musculus Expression profiling by high throughput sequencing 6 samples Submitted 2024/11/13 Platform GPL24247

Summary

Excessive Hedgehog (Hh) signaling activity contributes to fibrosis in multiple organs, however, its role in pancreatic stellate cell (PSC) activation and fibrosis development during chronic pancreatitis (CP) remains unclear. We demonstrate that GLI2 is upregulated in activated PSCs from CP patients and animal models. Specific deletion of Gli2, but not Smo, significantly alleviated fibrosis in CP models, indicating that CP is driven by non-canonical Hh signaling. Experiments on culture-activated primary PSCs reveal early nuclear translocation and increased GLI2 expression promptly after in vitro culture, with GLI2 being essential for PSC activation. SMO inhibition only reduces GLI2 activation in the short term, while activation of GLI2 by TGF-β/SMAD3 signaling explains the SMO-independent mechanisms leading to Hh activation in PSCs. Altogether, our data demonstrate the activation of the non-canonical Hh pathway in PSCs and indicate that GLI2 represents a promising therapeutic target for CP.

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Also filed as BioProject PRJNA1183842 and SRA study SRP544027. Searching any of these in the dataset finder brings you back here.

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