In addition we demonstrated that

In addition, we demonstrated that the combination of PCBP2 siRNA and LY2109761 had a potent silencing effect on collagen expression (Fig. 8). Both HSC-T6 Sorafenib manufacturer and primary HSCs were used to evaluate the combinational treatment. LY2109761, a TGFβ receptor type I/II kinase inhibitor, has been used to treat pulmonary fibrosis and human hypertrophic scar fibroblasts. It was reported that LY2109761 strongly inhibits pulmonary fibrosis. It was also found that LY2109761 reduces the expression of pSMAD1 and pSMAD2, and attenuates the gene expression involved in canonical and noncanonical TGF-β signaling. These data indicate that LY2109761 has an antifibrogenic effect through the inhibition of proinflammatory, proangiogenic and profibrotic signals. Furthermore, Wang et al. reported that LY2109761 suppresses the mRNA levels of type I collagen and TGF-β1 by approximately 86% and 85% in hypertrophic scar-derived fibroblasts, respectively. TGF-β1 enhances collagen expression through its cognate receptors to Smad proteins, which increases the transcription of their target genes including procollagen I and procollagen III. Here, we used LY2109761 combined with PCBP2 siRNA to suppress collagen synthesis and inhibit collagen stability, respectively, which produced a strongly synergistic silencing effect on the accumulation of type I collagen.
Conflict of interest
Acknowledgments This work was supported by an award (1R01AA021510) from the National Institutes of Health.