Abstract
BackgroundMicroRNAs (miRNAs) contribute to the progression of chronic kidney disease (CKD) by regulating renal homeostasis. This study explored the effects of miR-181a on CKD through the Toll-like receptor (TLR)/nuclear factor-kappa B (NF-κB) pathway by binding to CRY1.MethodsSeventy male rats were selected and assigned into specific groups: miR-181a mimic, miR-181a inhibitor, and siRNA against CRY1, with each group undergoing different treatments to investigate many different outcomes. First, 24-h urinary protein was measured. ELISA was used to determine the serum levels of SOD, ROS, MDA, IL-1β, IL-6, and TNF-α. Biochemical tests for renal function were performed to measure albumin, uric acid, and urea in urine and urea nitrogen and creatinine in serum. The glomerulosclerosis index (GSI) and renal tubular epithelial (RTE) cell apoptosis were detected using PASM staining and TUNEL staining, respectively. Finally, RT-qPCR and western blot were done to determine miR-181a, CRY1, TLR2, TLR4, and NF-κB expression.ResultsCRY1 is the target gene of miR-181a, according to a target prediction program and luciferase assay. Rats diagnosed with CKD presented increases in 24-h urinary protein; GSI; RTE cell apoptosis rate; serum ROS, MDA, IL-1β, IL-6, and TNF-α; and CRY1, TLR2, TLR4, and NF-κB expression, as well as decreases in SOD level and miR-181a expression. Following transfection with either the miR-181a mimic or si-CRY1, 24-h urinary protein, renal damage, GSI, and cell apoptosis rate were all decreased. In addition, the overexpression of miR-181a or inhibition of CRY1 alleviated the degree of kidney injury through suppression of the TLR/NF-κB pathway.ConclusionmiR-181a alleviates both GS and RTE injury in CKD via the down-regulation of the CRY1 gene and the TLR/NF-κB pathway.
Highlights
MicroRNAs contribute to the progression of chronic kidney disease (CKD) by regulating renal homeostasis
Up-regulated miR-181a or down-regulated CRY1 reduces urinary protein levels of CKD As seen in Fig. 2, the 24-h urinary protein at the end of the 4th week following transfection had significantly increased among the 6 CKD groups compared with the normal group (p < 0.05)
Up-regulating miR-181c protects kidneys from CsA-induced renal injury and fibrosis through the suppression of the epithelial-mesenchymal transition (EMT) (Sun et al 2017). Consistent with those findings, our study found that miR-181a inhibited both the GS and renal tubular epithelial (RTE) injury in CKD, which was supported by an apparent decrease in the cell apoptosis rate and the levels of ROS, MDA, IL-1β, IL-6, and TNF-α in the miR-181a mimic group
Summary
MicroRNAs (miRNAs) contribute to the progression of chronic kidney disease (CKD) by regulating renal homeostasis. Chronic kidney disease (CKD) is a highly prevalent public health problem, and its incidence is rapidly increasing worldwide. CKD is characterized by certain adverse outcomes, including cardiovascular disease (CVD), kidney function failure, and premature death (Levey et al 2005). CKD can be classified based on the stages of disease severity, which are evaluated by measuring the body’s glomerular filtration rate and albuminuria, as well as making a clinical diagnosis (Levey and Coresh 2012). Significant advances have been made in controlling the progression of CVD, but the incidence and prevalence of CKD are still alarmingly high rates (Gaddam et al 2016). A recent breakthrough has been the discovery that microRNAs (miRNAs), small non-coding RNA molecules, are involved in cancer (Lorenzen et al 2011)
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