MicroRNAs in renal fibrosis

Abstract

MicroRNAs (miRNAs) are endogenous short non-coding RNAs that regulate most of important cellular processes by inhibiting gene expression through the post-transcriptional repression of their target mRNAs. In kidneys, miRNAs have been associated in renal development, homeostasis, and physiological functions. Results from clinical and experimental animal studies demonstrate that miRNAs play essential roles in the pathogenesis of various renal diseases. Chronic kidney diseases (CKD) is characterized by renal fibrosis. Transforming growth factor beta (TGF-β) is recognized as a major mediator of renal fibrosis because it is able to stimulate the accumulation of extracellular matrix (ECM) proteins to impair normal kidney function. Recently, emerging evidence demonstrate the relationship between TGF-β signaling and miRNAs expression during renal diseases. TGF-β regulates expression of several microRNAs, such as miR-21, miR-192, miR-200, miR-433, and miR-29. MiR-21, miR-192, and miR-433 which are positively induced by TGF-β signaling play a pathological role in kidney diseases. In contrast, members in both miR-29 and miR-200 families which are inhibited by TGF-β signaling protect kidneys from renal fibrosis by suppressing the deposition of ECM and preventing epithelial-to-mesenchymal transition, respectively. Clinically, the presence of miRNAs in blood and urine has been examined to be early biomarkers for detecting renal diseases. From experimental animal studies of CKD, targeting microRNAs also provides evidence about therapeutic potential of miRNAs during renal diseases. Now, it comes to the stage to examine the exact mechanisms of miRNAs during the initiation and progression of renal diseases. Therefore, determining the function of miRNAs in renal fibrosis may facilitate the development of both early diagnosis and treatment of renal diseases.

Regulation of podoplanin expression by microRNA-29b associates with its antiapoptotic effect in angiotensin II-induced injury of human podocytes

“…Furthermore, they depicted that miR-29b expression was increased in patients with aneurysms [38]. Moreover, miR-29b was previously associated with 3'UTR of PDPN mRNA (dark grey ); miR-29b (light grey) renal fibrosis [18]. In contrast to the findings of Jeppesen et al, AngII was found to induce loss of miR-29b in kidney samples of a nephropathy mouse model with arterial hypertension [5].…”

Combining Extracellular miRNA Determination with Microfluidic 3D Cell Cultures for the Assessment of Nephrotoxicity: a Proof of Concept Study

“…Altered miRNA levels have been associated with the pathogenesis of various renal diseases, such as acute kidney injury and renal fibrosis (30,37). Also, circulating miRNAs and exosomal miRNAs are known to be released as a response to stress or during injury (38) and have been proposed to have great potential as biomarkers for prognosis and diagnosis of several diseases (39,40).…”

“…In vivo, mir-29a in serum correlates with the severity of acute kidney injury (12) and has also been associated with the modulation of early events that facilitate tissue remodeling in tendon (41). mir-192 and mir-34a have been associated with tissue fibrosis and apoptosis (32,33,37). mir-34a is induced in kidneys of mice (in vivo) and in a mouse proximal tubular cell, BUMPT-306 (in vitro) after cisplatin-induced activation of p53.…”

MicroRNA-483-3p Inhibits Extracellular Matrix Production by Targeting Smad4 in Human Trabecular Meshwork Cells

“…20 Meanwhile, it has been reported that miRNAs could regulate and maintain ECM homeostasis. [21][22][23] In HTM cells, miR-29b targets bone morphogenetic protein 1 (BMP1), ADAM12, and NKIRAS2 and downregulates multiple ECM components, including collagens, LAMC1, and FBN. 24,25 However, abnormal deposition of ECM is still not fully explored.…”