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.
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.
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.