Apelin inhibited epithelial−mesenchymal transition of podocytes in diabetic mice through downregulating immunoproteasome subunits β5i

Abstract

The epithelial−mesenchymal transition (EMT) of podocytes had been reported to be involved in the glomerular fibrosis in diabetic kidney diseases, which was regulated by TGFβ and NFκB pathways. And apelin, an adipokine which is upregulated in diabetic kidney diseases, was reported to be negatively correlated to TGFβ in polycystic kidney disease and attenuate EMT in renal tubular cells. Therefore, it is hypothesized that apelin might inhibit the EMT of podocytes through downregulating the expression and activation of TGFβ/Smad pathway in diabetic kidney diseases. The results showed that apelin in glomeruli of diabetic mice were increased and exogenous apelin inhibited the EMT of podocytes in diabetic mice, which were accompanied with the decreased expression of proteasome subunits β5i. The results from β5iKO mice confirmed that the inhibiting effects of apelin on EMT of podocytes in diabetic mice were dependent on β5i. The results from culture podocytes showed that apelin decreased the degradation of pIκB and promoted the translocation of IκB into nucleus through decreasing the expression of β5i, which would inhibit the promoting effects of NFκB on expression of TGFβ and followed by decreased activation of Smad pathway and EMT in podocytes. In conclusion, apelin might act as an EMT suppressor for podocytes to decrease the process of glomerular fibrosis in diabetic mice.

Neuropilin 1 modulates TGF‑β1‑induced epithelial‑mesenchymal transition in non‑small cell lung cancer

“…metastasis (37)(38)(39). Functional associated research between NRP1 and TGFβ1-induced EMT has also been carried out.…”

Roles of the Hepatic Endocannabinoid and Apelin Systems in the Pathogenesis of Liver Fibrosis

“…The apelin system displays major physiological roles in vascular and lymphatic development [155,156], in neurology [157], and in the digestive system [158]. The activation of the apelin system has demonstrated many beneficial effects in cardiovascular, kidney, skin, and metabolic diseases [128,142,150,159,160,161,162,163,164]. Apelin has aroused a special interest in the field of cardiology since it is one of the most powerful dose-dependent positive inotropic agents known to date, as demonstrated in perfused hearts [153].…”

Losartan through Hsp70 Avoids Angiotensin II Induced Mesenchymal Epithelial Transition Proximal Tubule Cells from Spontaneously Hypertensive Rats

“…Although most of the antioxidative effects of Losartan have been reported, a direct link between the Hsp70 chaperone and the epithelialmesenchymal transition (EMT) has not been widely studied in proximal tubule cells. Previous work supports that EMT is involved in renal pathogenesis, particularly in renal fibrosis [33,34]. EMT also plays an imperative role in renal interstitial fibrosis in diabetic nephropathy [35].…”