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Combined Inhibition of the TGF-β1/Smad Pathway by Prevotella copri And Lactobacillus murinus to Reduce Inflammation And Fibrosis in Primary Sclerosing Cholangitis
Shen, Y.; Jiang, B.; Zhang, C.; Wu, Q.; Li, L.; Jiang, P. Combined Inhibition of the TGF-β1/Smad Pathway by Prevotella copri and Lactobacillus murinus to Reduce Inflammation and Fibrosis in Primary Sclerosing Cholangitis. Int. J. Mol. Sci.2023, 24, 11010.
Shen, Y.; Jiang, B.; Zhang, C.; Wu, Q.; Li, L.; Jiang, P. Combined Inhibition of the TGF-β1/Smad Pathway by Prevotella copri and Lactobacillus murinus to Reduce Inflammation and Fibrosis in Primary Sclerosing Cholangitis. Int. J. Mol. Sci. 2023, 24, 11010.
Shen, Y.; Jiang, B.; Zhang, C.; Wu, Q.; Li, L.; Jiang, P. Combined Inhibition of the TGF-β1/Smad Pathway by Prevotella copri and Lactobacillus murinus to Reduce Inflammation and Fibrosis in Primary Sclerosing Cholangitis. Int. J. Mol. Sci.2023, 24, 11010.
Shen, Y.; Jiang, B.; Zhang, C.; Wu, Q.; Li, L.; Jiang, P. Combined Inhibition of the TGF-β1/Smad Pathway by Prevotella copri and Lactobacillus murinus to Reduce Inflammation and Fibrosis in Primary Sclerosing Cholangitis. Int. J. Mol. Sci. 2023, 24, 11010.
Abstract
Background: primary sclerosing cholangitis (PSC) is a chronic cholestatic disease characterized by inflammation and fibrosis of the bile ducts. Cholestasis may lead to hepatic inflammation and fibrosis, and amelioration of cholestasis may allow recovery from inflammatory and fibrotic pathological damage. Prevotella copri (P. copri) intervention have been reported could significantly improve cholestasis and liver fibrosis in DDC-induced PSC mice model. Despite alone P. copri treatment could not recover DDC-induced inflammation, it increased the abundance of Lactobacillus murinus (L. murinus) compared to DDC treatment, which has been reported to have anti-inflammatory effects. The abundance of L. murinus still not recover to normal level may underlie hepatic inflammation in P. copri+DDC mice. Method: alone or in combination interventions of P. copri and L. murinus were used to investigate the molecular mechanism of improvement of PSC inflammation and fibrosis. Results: P. copri and L. murinus significantly reduced the hepatic inflammatory cell aggregation and inflammatory factor expression, as well as the hepatic collagen content and fibrin factor expression in PSC mice. Further analysis of phosphorylation and dephosphorylation levels revealed that P. copri and L. murinus combined intervention in PSC mice inhibited the activity of DDC-activated TGF-β1/Smad pathway, thereby reducing liver inflammation and fibrosis. Conclusion: combination of P. copri and L. murinus inhibits the TGF-β1/Smad pathway and reduces inflammation and fibrosis in PSC.
Biology and Life Sciences, Immunology and Microbiology
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