Abstract
Diabetic kidney disease (DKD) has become the most common cause of chronic kidney disease. Proteinuria is generally considered one of the clinical indicators of renal damage, and it is also closely related to the progression of DKD. Accumulating evidence indicates that proteinuria induces an upregulation of the expression levels of inflammatory cytokines and fibrosis markers in renal tubular epithelial cells, but the mechanism remains unclear. Previously, we showed that early growth response 1 (Egr1) played a key role in renal tubular injury. However, the upstream mechanism of Egr1 in the development of DKD is poorly understood. In this study, we found that albumin stimulation significantly increased the expression levels of Egr1, interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), and fibronectin (FN) in HK-2 cells but decreased miR-23a-3p levels. We then identified that miR-23a-3p targeted the 3′ untranslated region (UTR) of Egr1 and directly suppressed the expression of Egr1. Moreover, we found that overexpression and inhibition of miR-23a-3p in HK-2 cells attenuated and promoted the expression of IL-6, TNF-α, and FN, respectively. Additionally, Egr1 silencing reversed the inflammation and fibrosis caused by the miR-23a-3p inhibitor. Thus, we conclude that miR-23a-3p attenuates the development of DKD through Egr1, suggesting that targeting miR-23a-3p may be a novel therapeutic approach for DKD.
Highlights
Diabetes is an important chronic disease worldwide (Liu et al 2019)
The expression of early growth response 1 (Egr1), interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), and FN is increased in Diabetic kidney disease (DKD) To explore the relationship between Egr1 and renal inflammation and fibrosis in DKD, we first detected the expression of Egr1, inflammatory cytokines, and the fibrotic marker in renal tissues of DKD mice
The Western blot results showed that the protein levels of Egr1, TNF-α, and FN significantly increased in the renal cortex of mice in the DKD group compared to the control group (Supplementary Fig. 1)
Summary
Diabetes is an important chronic disease worldwide (Liu et al 2019). According to the International Diabetes Federation (IDF), as of 2019, there were 463 million diabetic patients worldwide (International Diabetes Federation 2019). Diabetic kidney disease (DKD) is one of the most serious complications of diabetes. In China, DKD has surpassed chronic glomerulonephritis to become the most common cause of chronic kidney disease (CKD) (Zhang et al 2016). Proteinuria is an important marker of the occurrence and development of DKD and is used to evaluate the efficacy of treatment for DKD. Increasing evidence has shown that proteinuria may serve as an alternative endpoint for the study of Shuyue Sheng and Meina Zou contributed to this work
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