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Upregulation of MiR-126 Delays the Senescence of Human Glomerular Mesangial Cells Induced by High Glucose via Telomere-p53-p21-Rb Signaling Pathway

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Abstract

Diabetic kidney disease (DKD) is a microvascular complication of type 2 diabetes. The study of DKD mechanisms is the most important target for the prevention of DKD. Renal senescence is one of the important pathogeneses for DKD, but the mechanism of renal and cellular senescence is unclear. Decreased expression of circulating miR-126 is associated with the development of DKD and may be a promising blood-based biomarker for DKD. This study is to probe the effect and mechanism of miR-126 on the aging of human glomerular mesangial cells (HGMCs) induced by high glucose. HGMCs were cultured with Roswell Park Memorial Institute (RPMI-1640) in vitro. The effect of high glucose on morphology of HGMCs was observed 72 h after intervention. The cell cycle was examined by flow cytometry. The telomere length was measured by Southern blotting. The expression levels of p53, p21 and Rb proteins in p53-p21-Rb signaling pathway and p-stat1, p-stat3 in JAK/STAT signaling pathway were detected by Western blotting respectively. The expression of miR-126 was examined by qRT-PCR. MiR-126 mimics was transfected into HGMCs. The effects of miR-126 mimics transfection on cell morphology, cell cycle, telomere length, p53, p21, Rb, p-stat1 and p-stat3 were observed. The results showed that high glucose not only arrested the cell cycle in G1 phase but also shortened the telomere length. High glucose led to high expression of p53, p21, Rb, p-stat1 and p-stat3 and premature senescence of HGMCs by activating the telomere-p53-p21-Rb and JAK/STAT signaling pathways. Moreover, the miR-126 was decreased in HGMCs induced by high glucose. It was suggested that the transfection of miR-126 mimics could inhibit the telomere-p53-p21-Rb and JAK/STAT signaling pathway activity in vitro and delay the senescence of HGMCs. The results may serve as a new strategy for the treatment of DKD.

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Authors and Affiliations

  1. Department of Nephrology, Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, 210008, China

    Dong-wei Cao & Chun-ming Jiang

  2. Department of Nephrology, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008, China

    Dong-wei Cao, Chun-ming Jiang, Cheng Wan, Miao Zhang, Qing-yan Zhang & Min Zhao

  3. Department of Dermatology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China

    Bo Yang

  4. Department of Endocrinology, Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, 210008, China

    Da-long Zhu

  5. Basic Medical School, Nanjing Medical University, Nanjing, 210000, China

    Xiao Han

Authors
  1. Dong-wei Cao
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  2. Chun-ming Jiang
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  3. Cheng Wan
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  4. Miao Zhang
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  5. Qing-yan Zhang
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  6. Min Zhao
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  7. Bo Yang
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  8. Da-long Zhu
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  9. Xiao Han
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Corresponding authors

Correspondence to Da-long Zhu or Xiao Han.

Additional information

This project was supported by grants from the Key Science and Technology Development Program of Nanjing City of the People’s Republic of China (No. YKK15057 and No. YKK16097) and the National Natural Science Foundation of China (No. 81473684).

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Cao, Dw., Jiang, Cm., Wan, C. et al. Upregulation of MiR-126 Delays the Senescence of Human Glomerular Mesangial Cells Induced by High Glucose via Telomere-p53-p21-Rb Signaling Pathway. CURR MED SCI 38, 758–764 (2018). https://doi.org/10.1007/s11596-018-1942-x

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  • DOI: https://doi.org/10.1007/s11596-018-1942-x

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