Endocrine Abstracts

Background: Epithelial-mesenchymal transition (EMT) plays a key role in tubulointerstitial fibrosis, which is a hallmark of diabetic kidney disease (DKD). Our previous studies have shown that CRTC2 can regulate glucose metabolism and lipid metabolism at the same time. However, it is still unclear whether CRTC2 participates in the EMT process of DKD.

Methods: We used protein-protein network (PPI) analysis to determine differentially expressed genes in DKD and EMT. Then we constructed STZ plus high-fat diabetic mice model and used HK-2 cells that have been verified to confirm the bioinformatics research results. The efects of CRTC2 on epithelial-mesenchymal transition of diabetic kidney disease through the CREB-Smad2/3 signaling pathway were investigated in vivo and in vitro using Q-PCR, WB, IHC and double luciferase reporter gene experiments.

Results: Firstly, bioinformatics research showed that CRTC2 may promote the EMT process of diabetic renal tubules through the CREB-Smad2/3 signaling pathway. Furthermore, Western blot results showed that overexpressed CRTC2 could reduce the expression of E-cadherin. CRTC2 and α-SMA were increased in STZ mice. Luciferase activity of α-SMA, the key protein of EMT, was sharply increased in response to overexpressed CRTC2 and decreased by silencing in CREB and Smad2/3. In the Q-PCR experiment, the mRNA of α-SMA increased significantly when CRTC2 was overexpressed and decreased partly when CREB and Smad2/3 were silenced. However, E-cadherin had the opposite result.

Conclusion: This study demonstrated that CRTC2 activates the EMT process via the CREB-Smad2/3 signaling pathway in diabetic renal tubules.