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Objectives <p>To explore the regulation and function of serum response factor (SRF)/cysteine-rich protein 61 (Cyr61) pathway in renal tubular epithelial–myofibroblast transdifferentiation (EMyT) in the chronic progression after ischemic acute kidney injury (AKI).</p> Methods <p>The expression of SRF, Cyr61, myofibroblast markers (collagen-3, α-SMA and vimentin) and epithelial markers (E-cadherin and ZO-1) were examined in mouse renal tubular epithelial cells (TCMK-1 cells) under hypoxia/reoxygenation (H/R) treatment or rat renal medulla tissue samples after ischemia/reperfusion (I/R) treatment. SRF was overexpressed by pcDNA–SRF plasmid and suppressed by CCG-1423 (a small molecule inhibitor of SRF) or SRF siRNA to study how SRF influences renal tubular EMyT through Cyr61 in the chronic progression after AKI.</p> Results <p>In TCMK-1 cells under H/R treatment and renal medulla tissue from I/R rats, the SRF along with Cyr61, collagen-3, α-SMA and vimentin expression was upregulated, while E-cadherin and ZO-1 expression was downregulated. SRF upregulation in TCMK-1 cells increased Cyr61 expression. Blockade of SRF by an SRF-specific siRNA or CCG-1423 reduced Cyr61 induction, protected renal tubular epithelial cells from undergoing EMyT and improved the chronic progression after ischemic AKI both in vitro and in vivo.</p> Conclusions <p>Increased SRF/Cyr61 pathway activity promotes EMyT and dysfunction in renal tubular epithelial cells in the chronic progression after AKI. Targeting SRF with CCG-1423 may be an attractive therapeutic strategy in the chronic progression after AKI.</p>

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Serum response factor targets Cyr61 to facilitate chronic progression after ischemic acute kidney injury through renal tubular epithelial–myofibroblast transdifferentiation

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月24日

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  • Lin Che,
  • Lingyu Xu,
  • Chenyu Li,
  • Chen Guan,
  • Quandong Bu,
  • Congjuan Luo,
  • Hong Luan,
  • Bin Zhou,
  • Chengyu Yang,
  • Xiaofei Man,
  • Hui Zhang,
  • Yan Xu,
  • Long Zhao

摘要

Objectives

To explore the regulation and function of serum response factor (SRF)/cysteine-rich protein 61 (Cyr61) pathway in renal tubular epithelial–myofibroblast transdifferentiation (EMyT) in the chronic progression after ischemic acute kidney injury (AKI).

Methods

The expression of SRF, Cyr61, myofibroblast markers (collagen-3, α-SMA and vimentin) and epithelial markers (E-cadherin and ZO-1) were examined in mouse renal tubular epithelial cells (TCMK-1 cells) under hypoxia/reoxygenation (H/R) treatment or rat renal medulla tissue samples after ischemia/reperfusion (I/R) treatment. SRF was overexpressed by pcDNA–SRF plasmid and suppressed by CCG-1423 (a small molecule inhibitor of SRF) or SRF siRNA to study how SRF influences renal tubular EMyT through Cyr61 in the chronic progression after AKI.

Results

In TCMK-1 cells under H/R treatment and renal medulla tissue from I/R rats, the SRF along with Cyr61, collagen-3, α-SMA and vimentin expression was upregulated, while E-cadherin and ZO-1 expression was downregulated. SRF upregulation in TCMK-1 cells increased Cyr61 expression. Blockade of SRF by an SRF-specific siRNA or CCG-1423 reduced Cyr61 induction, protected renal tubular epithelial cells from undergoing EMyT and improved the chronic progression after ischemic AKI both in vitro and in vivo.

Conclusions

Increased SRF/Cyr61 pathway activity promotes EMyT and dysfunction in renal tubular epithelial cells in the chronic progression after AKI. Targeting SRF with CCG-1423 may be an attractive therapeutic strategy in the chronic progression after AKI.