Open Access

Trpc6 knockout protects against renal fibrosis by restraining the CN‑NFAT2 signaling pathway in T2DM mice

  • Authors:
    • Ran Sun
    • Min Han
    • Yan Liu
    • Yong Su
    • Qifeng Shi
    • Lei Huang
    • Liangliang Kong
    • Weizu Li
    • Weiping Li
  • View Affiliations

  • Published online on: November 27, 2023     https://doi.org/10.3892/mmr.2023.13136
  • Article Number: 13
  • Copyright: © Sun et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Diabetic kidney disease (DKD), one of the common complications of type‑2 diabetes mellitus (T2DM), has become the principal cause of end‑stage kidney disease. Transient receptor potential channel 6 (TRPC6), one of non‑selective cation channels with significant calcium‑permeability, is associated with renal fibrosis. However, the mechanism of TRPC6 in T2DM‑induced renal fibrosis is still not entirely understood. The present study explored the potential mechanism of Trpc6 knockout in T2DM‑induced renal fibrosis in Trpc6‑/‑ mice. The results showed that Trpc6 knockout inhibited the loss of body weight and the increase of fasting blood glucose (FBG) and significantly improved renal dysfunction and glomerular fibrosis in T2DM mice. The present study also indicated that Trpc6 knockout significantly lowered the expression of phosphorylated (p‑)SMAD2/3, TGF‑β, calcineurin (CN), nuclear factor of activated T‑cell (NFAT)2 and Nod‑like receptor (NLR) 3 inflammasome‑associated proteins. Calcium imaging results revealed that Trpc6 knockdown could decrease the levels of [Ca2+]i and inhibited calcium homeostasis imbalance. Moreover, it was found that knockout of Trpc6 had no significant influence on lipid disposition and reactive oxygen species generation in the kidney cortex. The present study suggested that knockout of Trpc6 may alleviate glomerular fibrosis and delay DKD progression by reducing [Ca2+]i overload and inhibiting the CN‑NFAT2 pathway in T2DM mice.
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January-2024
Volume 29 Issue 1

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

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Spandidos Publications style
Sun R, Han M, Liu Y, Su Y, Shi Q, Huang L, Kong L, Li W and Li W: <em>Trpc6</em> knockout protects against renal fibrosis by restraining the CN‑NFAT2 signaling pathway in T2DM mice. Mol Med Rep 29: 13, 2024
APA
Sun, R., Han, M., Liu, Y., Su, Y., Shi, Q., Huang, L. ... Li, W. (2024). <em>Trpc6</em> knockout protects against renal fibrosis by restraining the CN‑NFAT2 signaling pathway in T2DM mice. Molecular Medicine Reports, 29, 13. https://doi.org/10.3892/mmr.2023.13136
MLA
Sun, R., Han, M., Liu, Y., Su, Y., Shi, Q., Huang, L., Kong, L., Li, W., Li, W."<em>Trpc6</em> knockout protects against renal fibrosis by restraining the CN‑NFAT2 signaling pathway in T2DM mice". Molecular Medicine Reports 29.1 (2024): 13.
Chicago
Sun, R., Han, M., Liu, Y., Su, Y., Shi, Q., Huang, L., Kong, L., Li, W., Li, W."<em>Trpc6</em> knockout protects against renal fibrosis by restraining the CN‑NFAT2 signaling pathway in T2DM mice". Molecular Medicine Reports 29, no. 1 (2024): 13. https://doi.org/10.3892/mmr.2023.13136