Sox9 promotes renal tubular epithelial‑mesenchymal transition and extracellular matrix aggregation via the PI3K/AKT signaling pathway

  • Authors:
    • Zhiqiang Zhang
    • Wei Wu
    • Xiang Fang
    • Mei Lu
    • Heyan Wu
    • Chunlin Gao
    • Zhengkun Xia
  • View Affiliations

  • Published online on: September 2, 2020     https://doi.org/10.3892/mmr.2020.11488
  • Pages: 4017-4030
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Abstract

Sox9 is important for multiple aspects of development, such as testis, pancreas and heart development. Previous studies have reported that Sox9 induced epithelial‑mesenchymal transition (EMT) and extracellular matrix (ECM) production in organ fibrosis and associated diseases, such as vascular calcification. However, to the best of our knowledge, the role and underlying mechanism of action of Sox9 in renal fibrogenesis remains unknown. The results of the present study revealed that Sox9 expression levels were upregulated in the tubular epithelial cells of a rat model of obstructive nephropathy. Furthermore, the overexpression of Sox9 in NRK‑52E cells was discovered to promote renal tubular EMT and ECM aggregation, and these fibrogenic actions were potentiated by TGF‑β1. Notably, RNA‑sequencing analysis indicated the possible regulatory role of the PI3K/AKT signaling pathway in Sox9‑mediated renal tubular EMT and ECM aggregation. It was further demonstrated that the expression levels of phosphorylated AKT were upregulated in NRK‑52E cells overexpressing Sox9, while the PI3K inhibitors, LY29002 and wortmannin, inhibited the renal tubular EMT and ECM aggregation induced by the overexpression of Sox9 in NEK‑52E cells. In conclusion, the findings of the present study suggested that Sox9 may serve a profibrotic role in the development of renal tubular EMT and ECM aggregation via the PI3K/AKT signaling pathway. Therefore, Sox9 may be considered as a promising target for treating renal fibrosis.
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November-2020
Volume 22 Issue 5

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Zhang Z, Wu W, Fang X, Lu M, Wu H, Gao C and Xia Z: Sox9 promotes renal tubular epithelial‑mesenchymal transition and extracellular matrix aggregation via the PI3K/AKT signaling pathway. Mol Med Rep 22: 4017-4030, 2020
APA
Zhang, Z., Wu, W., Fang, X., Lu, M., Wu, H., Gao, C., & Xia, Z. (2020). Sox9 promotes renal tubular epithelial‑mesenchymal transition and extracellular matrix aggregation via the PI3K/AKT signaling pathway. Molecular Medicine Reports, 22, 4017-4030. https://doi.org/10.3892/mmr.2020.11488
MLA
Zhang, Z., Wu, W., Fang, X., Lu, M., Wu, H., Gao, C., Xia, Z."Sox9 promotes renal tubular epithelial‑mesenchymal transition and extracellular matrix aggregation via the PI3K/AKT signaling pathway". Molecular Medicine Reports 22.5 (2020): 4017-4030.
Chicago
Zhang, Z., Wu, W., Fang, X., Lu, M., Wu, H., Gao, C., Xia, Z."Sox9 promotes renal tubular epithelial‑mesenchymal transition and extracellular matrix aggregation via the PI3K/AKT signaling pathway". Molecular Medicine Reports 22, no. 5 (2020): 4017-4030. https://doi.org/10.3892/mmr.2020.11488