Exp Clin Endocrinol Diabetes 2019; 127(09): 630-640
DOI: 10.1055/s-0044-101601
Article
© Georg Thieme Verlag KG Stuttgart · New York

Klotho Restraining Egr1/TLR4/mTOR Axis to Reducing the Expression of Fibrosis and Inflammatory Cytokines in High Glucose Cultured Rat Mesangial Cells

Can Wu
1   Department of Endoscope, The First Hospital Affiliated to China Medical University, Shenyang, Liaoning, China
,
Xiaoyu Ma
2   Cadre Department, The First Hospital Affiliated to China Medical University, Shenyang, Liaoning, China
,
Yang Zhou
3   Department of Endocrinology, The First Hospital Affiliated to China Medical University, Shenyang, Liaoning, China
,
Yv Liu
3   Department of Endocrinology, The First Hospital Affiliated to China Medical University, Shenyang, Liaoning, China
,
Ying Shao
3   Department of Endocrinology, The First Hospital Affiliated to China Medical University, Shenyang, Liaoning, China
,
Qiuyue Wang
3   Department of Endocrinology, The First Hospital Affiliated to China Medical University, Shenyang, Liaoning, China
› Author Affiliations
Further Information

Publication History

received 03 October 2017
revised17 January 2018

accepted 23 January 2018

Publication Date:
11 June 2018 (online)

Abstract

Anti-aging protein Klotho is closely associated with a variety of chronic diseases and age-related diseases. And Klotho gene deficiency enhances the phosphorylation of mammalian target of rapamycin (mTOR), resulting in exacerbating streptozotocin-stimulated diabetic glomerular injury and promoting the progression of early diabetic kidney disease (DKD). However, it has not yet been elucidated that the mechanism of Klotho function on the pathogenesis of diabetic glomerular injury. What’s more, insulin represents the antilipolytic effect via the mTOR-early growth response factor 1 (Egr1) regulatory axis in mammalian organism. Valsartan reduced the high glucose-activated toll like report 4 (TLR4) expression and inflammatory cytokines via inhibiting Egr1 expression. In this study, we aim to explore the effects of Klotho on Egr1 expression and TLR4/mTOR pathways activity in high glucose cultured rat mesangial cells (RMCs) in vitro. Our study revealed that high glucose upregulated Egr1 to aggravate the inflammation and fibrosis in RMCs. And high glucose activates Egr1/TLR4/mTOR regulatory axis in MCs, indicating that one coherent feedforward loop is formed. Anti-aging protein Klotho may attenuate glomerular inflammation and fibrosis to provide protection against diabetic kidney injury via inhibiting the activity of Egr1/TLR4/mTOR regulatory axis in high glucose conditions. This study complements the function mechanism of Egr1/TLR4/mTOR regulatory axis playing in the pathogenesis of DKD, and provides a new direction and theoretical basis for anti-aging protein Klotho in DKD treatment.

 
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