ABSTRACT
Novel strategy for acid chlorides formation that do not use carboxylic acids is particularly attractive in chemical synthesis but remains challenging. Herein, we reported the development of a highly effective Pd-catalyzed hydrochlorocarbonylation of alkenes with CO for the formation of alkyl acid chlorides. Chlorosilane and AcOH were found as a mild HCl source for the reaction. The reaction shows broad substrate scope and produces both branched and linear alkyl acid chlorides in good to high yields upon different ligands and solvents. Cooperating with follow-up acylation reactions, the Pd-catalyzed hydrochlorocarbonylation offers a complementary platform for the synthesis of diverse carbonyl compounds from alkenes. Mechanistic investigations suggested that the reaction proceeded though a palladium hydride pathway, and CO prompted reductive elimination of the acyl-Pd-Cl intermediate.
ABSTRACT
TGF-ß1-induced excessive deposition of ECM and EMT process of tubular epithelial cells play critical roles in the development and progression of fibrosis in diabetic nephropathy (DN). Orai1 has been demonstrated to be involved in TGF-ß1-induced EMT via TGF-ß/Smad3 pathway. We are aimed to explore the effects of miR-93 on TGF-ß1-induced EMT process in HK2 cells. In this study, our data showed that miR-93 was dramatically decreased in renal tissues of patients with DN and TGF-ß1-stimulated HK2 cells. Moreover, the decreased level of miR-93 was closely associated with the increased expression of Orai1. Overexpression of miR-93 decreased Orai1 expression, and then suppressed TGF-ß1-mediated EMT and fibrogenesis. Next, we predicted that the Orai1 was a potential target gene of miR-93, and demonstrated that miR-93 could directly target Orai1. SiRNA targeting Orai1 was sufficient to suppress TGF-ß1-induced EMT and fibrogenesis in HK2 cells. Furthermore, Overexpression of Orai1 partially reversed the protective effect of miR-93 overexpression on TGF-ß1-mediated EMT and fibrogenesis in HK2 cells. Taken together, Orai1 and miR-93 significantly impact on the progression of TGF-ß1-mediated EMT and fibrogenesis in HK2 cells, and they may represent novel targets for the prevention strategies of fibrosis in the context of DN.
