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Research Paper|Volume 11, Issue 22|pp 10597—10609

Crucial role of serum response factor in renal tubular epithelial cell epithelial-mesenchymal transition in hyperuricemic nephropathy

Long Zhao1, Chenyu Li1, Bin Zhou1, Congjuan Luo1, Yanfei Wang1, Lin Che1, Jun Zhao2, Yan Xu1
  • 1Department of Nephrology, The Affiliated Hospital of Qingdao University, Qingdao 266003, China
  • 2Department of Nephrology, Shandong Weifang People’s Hospital, Weifang 261041, China
* Equal contribution
Received: August 15, 2019Accepted: November 8, 2019Published: November 27, 2019
https://doi.org/10.18632/aging.102479

Copyright © 2019 Zhao et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Objective: To explore the regulation and function of serum response factor (SRF) in epithelial-mesenchymal transition (EMT) in renal tubular epithelial cells (TECs) in hyperuricemic nephropathy (HN).

Results: In NRK-52E cells treated with UA and renal medulla tissue samples from hyperuricemic rats, SRF, fibronectin, α-SMA and FSP-1 expression was upregulated, while ZO-1 and E-cadherin expression was downregulated. SRF upregulation in NRK-52E cells increased slug expression. Blockade of SRF by an SRF-specific siRNA or CCG-1423 reduced slug induction and protected TECs from undergoing EMT both in vitro and in vivo.

Conclusion: Increased SRF activity promotes EMT and dysfunction in TECs in HN. Targeting SRF with CCG-1423 may be an attractive therapeutic strategy in HN.

Methods: The expression of SRF, mesenchymal markers (fibronectin, α-SMA, and FSP-1), epithelial markers (ZO-1 and E-cadherin) and was examined in rat renal TECs (NRK-52E cells) or renal medulla tissue samples following uric acid (UA) treatment. SRF overexpressed with pcDNA-SRF plasmid and suppressed by CCG-1423 (a small molecule inhibitor of SRF) to study how SRF influences EMT in TECs in HN. Oxonic acid (OA) was used to establish HN in rats.