Salt-inducible kinase 1 is involved in high glucose-induced mesangial cell proliferation mediated by the ALK5 signaling pathway

Yu,Jie; Hu,Xiaopeng; Yang,Zhengdong; Takemori,Hiroshi; Li,Yanhong; Zheng,Huan; Hong,Shicong; Liao,Qiuhong; Wen,Xiuying

doi:10.3892/ijmm.2013.1377

Salt-inducible kinase 1 is involved in high glucose-induced mesangial cell proliferation mediated by the ALK5 signaling pathway

Authors:
- Jie Yu
- Xiaopeng Hu
- Zhengdong Yang
- Hiroshi Takemori
- Yanhong Li
- Huan Zheng
- Shicong Hong
- Qiuhong Liao
- Xiuying Wen
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Affiliations: Department of Traditional Chinese Medicine and Endocrinology, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China, Department of General Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China, Department of Neurology, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China, Laboratory of Cell Signaling and Metabolism, National Institute of Biomedical Innovation, Osaka, Japan
Published online on: May 10, 2013 https://doi.org/10.3892/ijmm.2013.1377
Pages: 151-157

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Abstract

High glucose levels can induce mesangial cell proliferation and extracellular matrix (ECM) accumulation through the type I activin receptor-like kinase 5 (ALK5) signaling pathway. Salt-inducible kinase 1 (SIK1) prevents fibrosis by downregulating ALK5, while the expression level of the SIK1 protein itself is downregulated by glucose in neuronal cells following ischemia. In this study, we investigated the correlation between SIK1 and the ALK5 signaling pathway in a rat glomerular mesangial cell line (HBZY-1 cells). We found that high glucose levels downregulated the expression level of SIK1 and suppressed the phosphorylation of SIK1 at Thr-182. The downregulation of SIK1 by high glucose was accompanied by the activation of the ALK5 signaling pathway, while the overexpression of SIK1 in the HBZY-1 cells resulted in a decrease in the ALK5 protein level, as well in the levels of its downstream targets, including fibronectin and plasminogen activator inhibitor type I. In conclusion, high glucose may activate the ALK5 signaling pathway by downregulating SIK1, and SIK1 may be a protective factor against cellular proliferation and ECM accumulation in glomerular mesangial cells under high glucose conditions.

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