The mmu_circRNA_37492/hsa_circ_0012138 function as potential ceRNA to attenuate obstructive renal fibrosis

Abstract

Circular RNAs (circRNAs) are involved in the pathogenesis of certain renal diseases, however, the function and mechanism of them in renal fibrosis remains largely unknown. In the present study, RNA expression data in unilateral ureteral obstruction (UUO) kidneys was obtained from our previous circRNA Microarray and public Gene Expression Omnibus datasets to construct a ceRNA network. The effects of target circRNA as long as the homologous human circRNA on renal fibrosis was examined in vitro and in vivo. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was further performed among genes regulated by the human circRNA. We found that circRNA_37492, showing well connection degree in the ceRNA network, was abundant expression and high sequence conservation. We observed that the expression of circRNA_37492 was induced by the TGF-β1 or UUO in BUMPT cells and C57BL/6 mice, respectively. In vitro, cytoplasmic circRNA_37492 inhibited type I, III collagen and fibronectin deposition by sponging miR-7682-3p and then upregulated its downstream target Fgb. In vivo, overexpression of circRNA_37492 attenuated fibrotic lesions in the kidneys of UUO mice via targeting miR-7682-3p/Fgb axis. Furthermore, hsa_circ_0012138, homologous with circRNA_37492, may potentially target miR-651-5p/FGB axis in human renal fibrosis. Not only that, GO and KEGG enrichment revealed that hsa_circ_0012138-regulated genes were previously demonstrated to related to the fibrosis. In conclusion, we for the first time demonstrated that circRNA_37492 attenuated renal fibrosis via targeting miR-7682-3p/Fgb axis, and the homologous hsa_circRNA_0012138 was speculated as a possible ceRNA to regulate multiple gene expressions and involve in human renal fibrosis, suggesting that circRNA_37492/hsa_circ_0012138 may serve as potent therapy target for obstructive renal fibrosis disease.

Proximal tubular RAGE mediated the renal fibrosis in UUO model mice via upregulation of autophagy

“…The immunofluorescence of puncta was performed following the standard process. Whole BUMPT cell or kidney tissue protein lysates were separated through SDS-PAGE, and then transferred to membrane and subsequently exposed to primary antibodies of RAGE, STAT3, p-STAT3, α-SMA, Collagen I/III, fibronectin, vimentin, and Atg7 following by the second antibody according to the standard procedure [ 26 , 27 ].…”

Identification of an unrecognized circRNA associated with development of renal fibrosis

“…The OE of lncRNA 1700020I14Rik reduces the cell proliferation and expression of several genes (Col-4, FN, TGF-β1) associated with fibrosis by directly interacting with miR-34a-5p in a high glucose (HG) environment ( Li et al, 2018 ). Although circRNAs have been recognized as vital regulators in multiple diseases, few studies have revealed that the abnormal expressions of circRNAs are related to the RF ( Fan et al, 2021 ; Yi et al, 2021 ; Cheng et al, 2022 ). Hence, the role and regulatory mechanism of circRNAs in RF need urgently to be uncovered.…”

“…The circRNAs can also act as a miRNA sponge to regulate gene expression, and be associated with occurrence and development of RF. It indicated that overexpression (OE) of circRNA_37492 attenuated the TGF-β1/UUO-induced RF via targeting the miR-7682-3p/Fgb axis, while the homologous hsa_circRNA_0012138, as a possible competing endogenous RNA (ceRNA), was speculated to regulate multiple gene expressions in RF, suggesting that the circRNA_37492/hsa_circ_0012138 might act as a potential therapeutic target for obstructive RF ( Cheng et al, 2022 ). The circRNA_30032 was mediated UUO-induced and TGF-β1-induced RF by sponging miR-96-5p to up-regulate the expression of profibrotic proteins, including FN, indicating that this cirRNA could induce RF via the miR-96-5p/HBEGF/KRAS axis ( Yi et al, 2021 ).…”

Genome-Wide Analysis of Circular RNA-Mediated ceRNA Regulation in Porcine Skeletal Muscle Development

“…CircRNAs are abundant in transcriptomes and participate in various biological activities by regulating transcription, splicing, mRNA stability, and translation. At present, many studies have investigated circRNAs as potential therapeutic targets for various diseases [45][46][47]. With the ongoing development of related research strategies and methods, many biological functions of circRNAs in animals have also been emerging, and circRNAs have been found to regulate the proliferation and differentiation of animal skeletal muscle cells by acting as ceRNAs and encoding small peptides[48].…”