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.
Highlights
In recent years, the prevalence of hyperuricemia has increased rapidly worldwide, especially in coastal areas
serum response factor (SRF) expression was upregulated in renal medulla tissue samples from the hyperuricemic nephropathy (HN) rats (Figure 5), which was characterized by dramatic renal tubulointerstitial fibrosis
This study has demonstrated that SRF expression is increased in uric acid (UA)-induced tubular epithelial cells (TECs), which may play a critical part in promoting dysfunction and epithelial-mesenchymal transition (EMT)
Summary
The prevalence of hyperuricemia has increased rapidly worldwide, especially in coastal areas. The prevalence of hyperuricemia in American adults achieved 21.4% (21.6% in female and 21.1% in male) according to the National Health and Nutrition Examination Survey (NHANES) 2007–2008 [2]. From 2000 to 2014, as shown by a recent authoritative meta-analysis, the pooled prevalence of hyperuricemia of Chinese mainland was 13.3% (7.9% in female and 19.4% in male) [3]. Hyperuricemia is a serious health hazard that can lead to gouty arthritis, coronary heart disease, hypertension, diabetes and other metabolic syndrome-related diseases [4]. Patients with hyperuricemia have a 2.14 times higher risk of chronic kidney disease than those with normal UA levels [7]. It is of great clinical significance to explore the mechanism underlying hyperuricemic nephropathy (HN)
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