Hepatocarcinoma-intestine-pancreas/pancreatitis-associated protein (HIP/PAP) confers protection against hepatic fibrosis through downregulation of transforming growth factor β receptor II.
In conclusion, the results of the present study revealed that miR‑219 may regulate pro‑fibrotic markers by directly targeting the TGFBR2 gene and the miR‑219/TGFBR2 signaling pathway may be a potential therapeutic target for liver fibrosis.
After recombinant lentiviral particles were delivered into the liver via tail-vein injection, therapeutic amiRNAs were preferentially expressed in HSCs and efficiently co-knocked down in situ Tgfbr2 and Pdgfrβ expression, which correlates with downregulated expression of target or effector genes of their signaling, which include Pai-1, P70S6K, and D-cyclins. amiRNA-based HSC-specific co-silencing of Tgfbr2 and Pdgfrβ significantly suppressed hepatic expression of fibrotic markers α-Sma and Col1a1, extracellular matrix regulators Mmps and Timp1, and phenotypically ameliorated liver fibrosis, as indicated by reductions in serum alanine aminotransferase activity, collagen deposition, and α-Sma-positive staining.
Treatment with either an anti-αVβ6 blocking antibody or soluble transforming growth factor-β receptor type II reduced liver fibrosis in mice fed the ANIT diet.