MicroRNA and nephropathy: emerging concepts
Arthur CK Chung,1,3 Xueqing Yu,2 Hui Y Lan1,3
1Li Ka Shing Institute of Health Sciences and Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, People's Republic of China; 2Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China; 3CUHK Shenzhen Research Institute, Shenzhen, People's Republic of China
Abstract: Micro ribonucleic acids (miRNAs) are short noncoding RNAs that inhibit gene expression through the post-transcriptional repression of their target mRNAs. Increasing evidence shows that miRNAs have emerged as key players in diverse biologic processes. Aberrant miRNA expression is also closely related to various human diseases, including kidney diseases. From clinical and experimental animal studies, emerging evidence demonstrates a critical role for miRNAs in renal pathophysiology. Renal fibrosis is the hallmark of various chronic kidney diseases and transforming growth factor beta (TGF-β) is recognized as a vital mediator of renal fibrosis because it can induce production of extracellular matrix proteins resulting in dysfunction of the kidneys. The relationship between TGF-β signaling and miRNAs expression during renal diseases has been recently established. TGF-β positively or negatively regulates expression of several miRNAs, such as miR-21, miR-192, miR-200, and miR-29. Both miR-192 and miR-21 are positively regulated by TGF-β 1/Smad3 signaling and play a pathological role in kidney diseases. Conversely, members of both miR-29 and miR-200 families are negatively regulated by TGF-β/Smad3 and play a protective role in renal fibrosis by inhibiting the deposition of extracellular matrix and preventing epithelial-to-mesenchymal transition, respectively. Clinically, levels of miRNAs in circulation and urine may be potential biomarkers for detecting early stages of renal diseases and targeting miRNAs also provides promising therapeutic effects in rodent models of chronic kidney disease. However, mechanisms and roles of miRNAs under disease conditions remain to be explored. Thus, understanding the function of miRNAs in the pathogenesis of kidney diseases may offer an innovative approach for both early diagnosis and treatment of renal diseases.
Keywords: microRNAs, kidney diseases, renal fibrosis, TGF-β signaling
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