<p>Kidney tissue injury is clinically very common, and how to effectively repair renal damage is a critical scientific issue that urgently requires attention. This study focuses on exploring alternative therapeutic strategies for renal repair. Specifically, it aims to compare the differentiation capabilities of metanephric mesenchymal cells (MMC), bone marrow mesenchymal stem cells (BMSC), and adipose-derived mesenchymal stem cells (AMSC) into epithelial cells, and to investigate the role and mechanism of catalpol, an active component of the traditional Chinese medicine <i>Rehmannia glutinosa</i>, in enhancing the epithelial differentiation of MMC. The epithelial differentiation potential of AMSC, BMSC, and MMC was compared under epithelial induction medium with or without catalpol supplementation. MMC were cultured in epithelial induction medium, and the expression of epithelial marker E-Cadherin, mesenchymal markers α-SMA and renal epithelial-specific marker AQP2 were assessed using Western Blot and immunofluorescence staining to evaluate the epithelial differentiation capacity of MMC and the enhancing effect of catalpol. RNA-seq was performed to identify signaling pathways activated by catalpol in MMC. The canonical Wnt pathway inhibitor MSAB was added to determine whether the pro-epithelial differentiation effect of catalpol was inhibited. AMSC and BMSC exhibited limited epithelial differentiation potential, which was not enhanced by catalpol. Under epithelial induction medium, MMC differentiated into epithelial cells, with increased expression of E-Cadherin and decreased expression of α-SMA. Catalpol further enhanced this effect and promoted the expression of the renal epithelial marker AQP2. RNA-seq revealed that the canonical Wnt pathway was activated in MMC. The pro-epithelial differentiation effect of catalpol was inhibited by MSAB, accompanied by decreased expression of E-Cadherin and AQP2 and increased expression of α-SMA. Catalpol promotes the differentiation of MMC into renal epithelial cells by activating the canonical Wnt pathway.</p>

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Canonical Wnt pathway mediates catalpol-induced epithelial differentiation of porcine metanephric mesenchymal cells

  • Pengcheng Ji,
  • Yuansheng Xie,
  • Guangrui Geng,
  • Wenkai Guo,
  • Jingru Bi,
  • Bing Han,
  • Xu Wang,
  • Bo Fu

摘要

Kidney tissue injury is clinically very common, and how to effectively repair renal damage is a critical scientific issue that urgently requires attention. This study focuses on exploring alternative therapeutic strategies for renal repair. Specifically, it aims to compare the differentiation capabilities of metanephric mesenchymal cells (MMC), bone marrow mesenchymal stem cells (BMSC), and adipose-derived mesenchymal stem cells (AMSC) into epithelial cells, and to investigate the role and mechanism of catalpol, an active component of the traditional Chinese medicine Rehmannia glutinosa, in enhancing the epithelial differentiation of MMC. The epithelial differentiation potential of AMSC, BMSC, and MMC was compared under epithelial induction medium with or without catalpol supplementation. MMC were cultured in epithelial induction medium, and the expression of epithelial marker E-Cadherin, mesenchymal markers α-SMA and renal epithelial-specific marker AQP2 were assessed using Western Blot and immunofluorescence staining to evaluate the epithelial differentiation capacity of MMC and the enhancing effect of catalpol. RNA-seq was performed to identify signaling pathways activated by catalpol in MMC. The canonical Wnt pathway inhibitor MSAB was added to determine whether the pro-epithelial differentiation effect of catalpol was inhibited. AMSC and BMSC exhibited limited epithelial differentiation potential, which was not enhanced by catalpol. Under epithelial induction medium, MMC differentiated into epithelial cells, with increased expression of E-Cadherin and decreased expression of α-SMA. Catalpol further enhanced this effect and promoted the expression of the renal epithelial marker AQP2. RNA-seq revealed that the canonical Wnt pathway was activated in MMC. The pro-epithelial differentiation effect of catalpol was inhibited by MSAB, accompanied by decreased expression of E-Cadherin and AQP2 and increased expression of α-SMA. Catalpol promotes the differentiation of MMC into renal epithelial cells by activating the canonical Wnt pathway.