TGF-β1 inhibits the autophagy of podocytes by activating mTORC1 in IgA nephropathy

IgA nephropathy (IgAN) is a mesangial proliferative glomerulonephritis which often shows proteinuria, an indicator for podocyte damage. TGF-β1 has been known to contribute to podocyte injury by inducing apoptosis, cytoskeleton relocation or cytoskeleton loss. And Decorin, a small proteoglycan known to neutralize TGF-β1, was reported to induce autophagy in vascular endothelial cells. However, it remains unknown how TGF-β1 and Decorin can affect podocyte autophagy in mesangial proliferative glomerulonephritis. In this study, we used in vivo and in vitro models to find out the effect of TGF-β1 and Decorin on podocyte autophagy. P-rpS6 and p-ULK1 were detected by Western blot to show the activation of mTORC1 pathway following TGF-β1 treatment. Also, we collected serum from IgAN patients and anti-Thy1.1 nephritis, and quantified TGF-β1 and Decorin using ELISA. Together, we showed that TGF-β1 could activate mTORC1 and inhibit autophagy, while Decorin has precisely the opposite effect. As the mesangial cells (MCs) proliferate, TGF-β1 increases and Decorin decreases in the serum of IgAN and anti-Thy1.1 nephritis. This finding deepened our understanding regarding how MC proliferation could finally result in podocyte dysfunction. [Display omitted] •TGF-β1 inhibited the podocyte autophagy and activated mTOR pathway.•TGF-β/Smad2 was activated in the podocytes during MC proliferation.•Decorin neutralized the effect of TGF-β1 on the podocytes.