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

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, ?-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, ?-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.

SUBMITTER: Zhao L 

PROVIDER: S-EPMC6914413 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature