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Inhibition of STIM1 alleviates high glucose-induced proliferation and fibrosis by inducing autophagy in mesangial cells

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Abstract

Diabetic nephropathy (DN) is a renal microvascular complication caused by diabetes mellitus. One of the most typical characteristics of DN is glomerular mesangial cells (GMCs) proliferation. Stromal interaction molecule 1 (STIM1), a Ca2+ channel, is involved in many diseases. In this study, we investigated the role of STIM1 in the proliferation and fibrosis in high glucose (HG)-induced HBZY-1 cells. We found that the expression of STIM1 was increased in renal tissues of diabetic rat and HBZY-1 cells stimulated by HG. Downregulation of STIM1-mediated SOCE suppressed hyperglycemic cell proliferation and fibrosis by activating autophagy. In addition, the inhibitory effect of downregulating STIM1 on cells was blocked by autophagy inhibitor Bafilomycin A1 (BafA1). Moreover, this experiment also showed that STIM1 regulated autophagy, cell proliferation and fibrosis via PI3K/AKT/mTOR signal pathway. These results clarify the role of STIM1 in HBZY-1 cells and its mechanism, and provide a new target for the treatment of DN.

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Data Availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Abbreviations

DN:

Diabetic nephropathy

GMCs:

Glomerular mesangial cells

STIM1:

Stromal interaction molecule 1

TRPC3:

Transient receptor potential channel 3

TRPC6:

Transient receptor potential channel 6

HG:

High glucose

BafA1:

Bafilomycin A1

ECM:

Extracellular matrix

SOCE:

Stored-operated calcium entry

ASMCs:

Airway smooth muscle cells

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Funding

This work was supported by the National Natural Science Foundation of China Grants 31171087 and 30970662 (to Y.L.), the National Natural Science Foundation of China Grants 81172786, Health Committee of Hubei Province of China Grants WJ2019M146 and Chen Xiao-Ping Foundation CXPJJH11900018-06 (to M.Z.).

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Authors and Affiliations

  1. Department of Anatomy, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, 430030, Hubei, People’s Republic of China

    Xixi Zeng, Anbang Sun & Yanhong Liao

  2. Department of Emergency Surgery, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, 430030, Hubei, People’s Republic of China

    Weiyi Cheng

  3. Medical College, Affiliated Hospital, Hebei University of Engineering, Handan, People’s Republic of China

    Xin Hou

  4. Department of Thoracic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China

    Min Zhu

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  1. Xixi Zeng
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  4. Xin Hou
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  5. Min Zhu
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Contributions

YL, MZ and XZ conceived and designed research. XZ and AS drafted the manuscript and performed experiments. WC and XH contributed to the interpretation of the results. YL and MZ contributed to analyze data and prepare the manuscript. All authors contributed to revise the article and approved the submitted version.

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Correspondence to Min Zhu or Yanhong Liao.

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Zeng, X., Sun, A., Cheng, W. et al. Inhibition of STIM1 alleviates high glucose-induced proliferation and fibrosis by inducing autophagy in mesangial cells. Mol Cell Biochem (2023). https://doi.org/10.1007/s11010-023-04844-7

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