Dataset Information

Apelin inhibited epithelial-mesenchymal transition of podocytes in diabetic mice through downregulating immunoproteasome subunits ?5i.

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 TGF? and NF?B pathways. And apelin, an adipokine which is upregulated in diabetic kidney diseases, was reported to be negatively correlated to TGF? 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 TGF?/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 ?5i. The results from ?5iKO mice confirmed that the inhibiting effects of apelin on EMT of podocytes in diabetic mice were dependent on ?5i. The results from culture podocytes showed that apelin decreased the degradation of pI?B and promoted the translocation of I?B into nucleus through decreasing the expression of ?5i, which would inhibit the promoting effects of NF?B on expression of TGF? 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.

SUBMITTER: Yin J

PROVIDER: S-EPMC6178343 | biostudies-other | 2018 Oct

REPOSITORIES: biostudies-other

ACCESS DATA

Publications

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

Yin Jiming J Wang Yangjia Y Chang Jing J Li Bin B Zhang Jia J Liu Yu Y Lai Song S Jiang Ying Y Li Huihua H Zeng Xiangjun X

Cell death & disease 20181009 10

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 expressi ...[more]

PMID: 30301930

Similar Datasets

Project description:Purpose:Renal injury with the loss of podocyte was characteristic pathology of diabetic nephropathy (DN) and correlated with increased albuminuria. Many studies have found the nephroprotective effect of the novel inhibitors of sodium-glucose cotransporter 2 (SGLT2-is), like Dapagliflozin, delaying the progression of DN. However, the underlying mechanisms of SGLT2 associated with podocyte injury are still not fully elucidated. Methods: Through mRNA sequencing, streptozotocin-induced and Dapagliflozin-intraperitoneal injection mice models were established to explore potential mechanism between Dapagliflozin and renal phenotype. And all changes referring this observed pathway were proven repeatedly in podocyte. Results: Here, we generated the streptozotocin-induced DN models and found the accumulation of nephrotoxin and pathological lesions of the kidney, including interstitial inflammatory infiltration, mesangial expansion and glomerular sclerosis, while low expression of SGLT2 mitigated these injuries in Dapagliflozin-treated mice. Moreover, mRNA expression profile in these treated models determined the significance of insulin-like growth factor-1 receptor (IGF1R)/PI3K regulatory axis in glomerular injury. Particularly, SGLT2-is inhibited the increase of mesenchymal marker, α-SMA and the decrease of podocyte marker, nephrin at the gene or protein level. KEGG analysis also showed the enrichment of phosphatidylinositol signaling system and TGF-β/smad pathway. In parallel, the protein level of IGF1R, phosphorylated PI3K, and α-SMA were increased in high-glucose stimulated human podocyte, and reduced in Dapagliflozin (50nM and 100nM) or OSI-906 (inhibitor of IGF1R, 60nM) used groups. Notably, combination of the two inhibitors produced an accumulative effect in the protection of podocyte integrity. Mechanistically, IGF1 or IGF2 could bind to IGF1 receptors to mediate the epithelial-mesenchymal transition (EMT) of diabetic podocyte in response to the upregulation of SGLT2. Indeed, we enrolled the urine and plasma samples from a cohort consisting of 13 healthy people, and a cohort of 19 patients with DN using SGLT2-inhibitors (n=9) or not (n=10). Compared with pure DN patients, Elisa results suggested an increased circulation and excretion level of IGF1/2 in SGLT2-is used DN cohort. Conclusions: Taken together, our study reported the key role of SGLT2/IGF1R/PI3K signaling in regulating podocyte EMT. Modulating the IGF1R expression may provide a novel idea for DN therapy.

Dataset Information

Apelin inhibited epithelial-mesenchymal transition of podocytes in diabetic mice through downregulating immunoproteasome subunits ?5i.

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets