MiR-92d-3p suppresses the progression of diabetic nephropathy renal fibrosis by inhibiting the C3/HMGB1/TGF-β1 pathway.

Yuhua Zhang

doi:10.1042/bsr20203131

Abstract

The pathogenesis of diabetic nephropathy (DN) has not been fully elucidated. MicroRNAs (miRNAs) play an important role in the onset and development of DN renal fibrosis. Thus, the present study aimed to investigate the effect of miR-92d-3p on the progression of DN renal fibrosis. We used qRT-PCR to detect the expression levels of miR-92d-3p in the kidneys of patients with DN. Then, after transfecting lentiviruses containing miR-92d-3p into the kidneys of a DN mouse model and HK-2 cell line, we used qRT-PCR to detect the expression levels of miR-92d-3p, C3, HMGB1, TGF-β1, α-SMA, E-cadherin, and Col I. The expression levels of interleukin (IL) 1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α) in the HK-2 cells were detected through enzyme-linked immunosorbent assay (ELISA), and Western blotting and immunofluorescence were used in detecting the expression levels of fibronectin, α-SMA, E-cadherin, and vimentin. Results showed that the expression levels of miR-92d-3p in the kidney tissues of patients with DN and DN animal model mice decreased, and C3 stimulated HK-2 cells to produce inflammatory cytokines. The C3/HMGB1/TGF-β1 pathway was activated, and epithelial-to-interstitial transition (EMT) was induced in the HK-2 cells after human recombinant C3 and TGF-β1 protein were added. miR-92d-3p inhibited inflammatory factor production by C3 in the HK-2 cells and the activation of the C3/HMGB1/TGF-β1 pathway and EMT by C3 and TGF-β1. miR-92d-3p suppressed the progression of DN renal fibrosis by inhibiting the activation of the C3/HMGB1/TGF-β1 pathway and EMT.

Highlights

Chronic kidney disease (CKD) is a heterogeneous group of disorders
QRT-PCR was used in detecting the expression levels of component 3 (C3) (Figure 1B), HMGB1 (Figure 1C), TGF-β1 (Figure 1D), E-cadherin (Figure 1E), α-SMA (Figure 1F), and Col I (Figure 1G)
Blood glucose levels (Figure 2A) and urine protein levels (Figure 2B) significantly increased compared with those in the control group, indicating that Diabetic nephropathy (DN) mouse model was successfully established. qRT-PCR was used in detecting the expression levels of miR-92d-3p (Figure 2C), C3 (Figure 2D), HMGB1 (Figure 2E), TGF-β1 (Figure 2F), E-cadherin (Figure 2G), α-SMA (Figure 2H), and Col I (Figure 2I) in the kidney tissues of two groups of mice

Summary

Introduction

According to the current U.S Centers for Disease Control and Prevention (CDC) statistics, 37 million people in the United States are estimated to have CKD. The prevalence of type 2 diabetes (T2DM) shows an increasing trend yearly. Statistics from the International Diabetes Federation showed that the number of patients with T2DM may exceed 600 million by 2035. Diabetic nephropathy (DN) is one of the microvascular complications of T2DM and the most common cause of end-stage renal disease [1,2]. MicroRNAs (miRNAs) are small noncoding RNA molecules that regulate gene expression and are involved in the onset and development of tubular interstitial sclerosis and end-stage glomerular lesions that occur in various forms in CKD [3].

Methods

Results

Conclusion