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Calpain 6 inhibits autophagy in inflammatory environments: A preliminary study on myoblasts and a chronic kidney disease rat model

  • Authors:
    • Yue Yue Zhang
    • Li Jie Gu
    • Nan Zhu
    • Ling Wang
    • Min Chao Cai
    • Jie Shuang Jia
    • Shu Rong
    • Wei Jie Yuan
  • View Affiliations / Copyright

    Affiliations: Division of Nephrology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200080, P.R. China
    Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 194
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    Published online on: August 24, 2021
       https://doi.org/10.3892/ijmm.2021.5027
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Abstract

A non‑classical calpain, calpain 6 (CAPN6), can inhibit skeletal muscle differentiation and regeneration. In the present study, the role of CAPN6 in the regulation of the autophagy of myoblasts in vitro was investigated. The underlying molecular events and the CAPN6 level in atrophic skeletal muscle in a rat model of chronic kidney disease (CKD) were also investigated. In vitro, CAPN6 was overexpressed, or knocked down, in rat L6 myoblasts to assess autophagy and related gene expression and co‑localization. Subsequently, myoblasts were treated with a mixture of cytokines, and relative gene expression and autophagy were assessed. A rat model of CKD for muscle atrophy was established, and blood chemical level and the expression of CAPN6 in muscle were assessed. The data revealed that the knockdown of CAPN6 in rat myoblasts resulted in increased microtubule‑associated protein 1 light chain 3 (LC3) levels, while its overexpression decreased LC3 levels and impaired autophagy. Additionally, it was observed that the co‑localization of mammalian target of rapamycin (mTOR) and lysosomal‑associated membrane protein 1 (LAMP1), a lysosomal marker, proteins was increased. In addition, mTOR, Raptor and α‑tubulin (a marker of microtubules) increased in the CAPN6 overexpression group. However, inflammatory cytokines, such as interleukin (IL)‑6, tumor necrosis factor (TNF)‑α, interferon (INF)‑γ and lipopolysaccharides upregulated CAPN6 expression, inhibited L6 myoblast autophagy and stabilized mTOR activity. Furthermore, the animal model successfully mimicked human disease as regards an increase in body weight, and a reduction in muscle mass, cross‑sectional area and blood biomarker concentrations; a slight increase in CAPN6 mRNA and protein levels in muscles was observed. Finally, the data of the present study suggested that CAPN6 reduced autophagy via the maintenance of mTOR signaling, which may play a role in CKD‑related muscle atrophy. However, future studies are required to determine whether CAPN6 may be used as an intervention target for CKD‑related skeletal muscle atrophy.
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Copy and paste a formatted citation
Spandidos Publications style
Zhang YY, Gu LJ, Zhu N, Wang L, Cai MC, Jia JS, Rong S and Yuan WJ: Calpain 6 inhibits autophagy in inflammatory environments: A preliminary study on myoblasts and a chronic kidney disease rat model. Int J Mol Med 48: 194, 2021.
APA
Zhang, Y.Y., Gu, L.J., Zhu, N., Wang, L., Cai, M.C., Jia, J.S. ... Yuan, W.J. (2021). Calpain 6 inhibits autophagy in inflammatory environments: A preliminary study on myoblasts and a chronic kidney disease rat model. International Journal of Molecular Medicine, 48, 194. https://doi.org/10.3892/ijmm.2021.5027
MLA
Zhang, Y. Y., Gu, L. J., Zhu, N., Wang, L., Cai, M. C., Jia, J. S., Rong, S., Yuan, W. J."Calpain 6 inhibits autophagy in inflammatory environments: A preliminary study on myoblasts and a chronic kidney disease rat model". International Journal of Molecular Medicine 48.4 (2021): 194.
Chicago
Zhang, Y. Y., Gu, L. J., Zhu, N., Wang, L., Cai, M. C., Jia, J. S., Rong, S., Yuan, W. J."Calpain 6 inhibits autophagy in inflammatory environments: A preliminary study on myoblasts and a chronic kidney disease rat model". International Journal of Molecular Medicine 48, no. 4 (2021): 194. https://doi.org/10.3892/ijmm.2021.5027
Copy and paste a formatted citation
x
Spandidos Publications style
Zhang YY, Gu LJ, Zhu N, Wang L, Cai MC, Jia JS, Rong S and Yuan WJ: Calpain 6 inhibits autophagy in inflammatory environments: A preliminary study on myoblasts and a chronic kidney disease rat model. Int J Mol Med 48: 194, 2021.
APA
Zhang, Y.Y., Gu, L.J., Zhu, N., Wang, L., Cai, M.C., Jia, J.S. ... Yuan, W.J. (2021). Calpain 6 inhibits autophagy in inflammatory environments: A preliminary study on myoblasts and a chronic kidney disease rat model. International Journal of Molecular Medicine, 48, 194. https://doi.org/10.3892/ijmm.2021.5027
MLA
Zhang, Y. Y., Gu, L. J., Zhu, N., Wang, L., Cai, M. C., Jia, J. S., Rong, S., Yuan, W. J."Calpain 6 inhibits autophagy in inflammatory environments: A preliminary study on myoblasts and a chronic kidney disease rat model". International Journal of Molecular Medicine 48.4 (2021): 194.
Chicago
Zhang, Y. Y., Gu, L. J., Zhu, N., Wang, L., Cai, M. C., Jia, J. S., Rong, S., Yuan, W. J."Calpain 6 inhibits autophagy in inflammatory environments: A preliminary study on myoblasts and a chronic kidney disease rat model". International Journal of Molecular Medicine 48, no. 4 (2021): 194. https://doi.org/10.3892/ijmm.2021.5027
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