Abstract: FR-PO338
Critical Role of Serum Response Factor in Podocyte Epithelial-Mesenchymal Transition of Diabetic Nephropathy
Session Information
- Diabetic Kidney Disease: Basic - I
November 03, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Diabetic Kidney Disease
- 701 Diabetic Kidney Disease: Basic
Authors
- Zhao, Long, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China
- Xu, Yan, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China
Background
To investigate the expression and function of serum response factor (SRF) in podocyte epithelial–mesenchymal transition (EMT) of diabetic nephropathy (DN).
Methods
Expression of SRF, pSRF, synaptopodin, P-cadherin, ZO-1, α-SMA, FSP-1, fibronectin and collagen-1 were examined in podocytes or renal cortex following high glucose. SRF was upregulated by SRF plasmids and downregulated by CCG-1423 to investigate how SRF influence podocyte EMT in DN. Streptozocin was used to generate DM in rats.
Results
In podocytes after high glucose treatment, SRF, pSRF, α-SMA, FSP-1, fibronectin and collagen-1 increased, while synaptopodin, P-cadherin and ZO-1 declined. In vivo, CCG-1423 significantly abrogated the reduction of synaptopodin expression and the induction of SRF, collagen-1, α-SMA and FSP-1 expression in renal cortex tissues. Masson and PAS staining demonstrated that renal glomerular fibrosis was present in DM group, and after 8 weeks treatment with CCG-1423, renal glomerular fibrosis was dramatically ameliorated. In addition, CCG-1423 significantly preserved P-cadherin expression and suppressed α-SMA and FN expression in DN rats. SRF overexpression in podocytes induced expression of Snail, an important transcription factor that mediates EMT. Blockade of SRF reduced Snail induction, protected podocyte from EMT and improved proteinuria and serum albumin.
Conclusion
Together, increased SRF activity provokes podocytes EMT and dysfunction in DN. Targeting SRF by small molecule inhibitor may be an attractive therapeutic strategy for DN.