CircRNA_30032 promotes renal fibrosis in UUO model mice via miRNA-96-5p/HBEGF/KRAS axis

Lee, Yi; Ai, Kai; Li, Huiling; Qiu, Shuangfa; Li, Yijian; Wang, Yinhuai; Li, Xiaozhou; Zheng, Peilin; Chen, Junxiang; Wu, Dengke; Xiang, Xudong; Chai, Xiangping; Yuan, Yunchang; Zhang, Dongshan

doi:10.18632/aging.202947

Cited by 22 publications

(20 citation statements)

References 49 publications

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“…CircRNA_33702 was one of the most highly expressed circRNA in the kidney tissues and showed a 8.92- and 15.55-fold higher expression in the UUO group on days 3 and 7, respectively, compared to the sham group. (24) To investigate the expression site of circRNA_33702, BUMPT cells were treated with TGF-β1 before being subjected to FISH analysis. The cell nuclei were stained by DAPI, while 18S rRNA (cytoplasmic positive) and circRNA_33702 were labeled with CY3.…”

Section: Resultsmentioning

confidence: 99%

CircRNA_33702 promotes renal fibrosis by targeting the miR-29b-3p/WISP1 pathway

Lee

Wang

2022

Preprint

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Growing evidence suggest that circular RNAs (circRNAs) are critical mediators in renal diseases. However, there have been very few reports about the role of circRNAs in renal fibrosis. In this study, circRNA_33702 was found to be upregulated, both in UUO mice and in TGF-β1-treated BUMPT cells. Whilst knockdown of circRNA_33702 was shown to relieve the TGF-β1-induced expression of collagen I, collagen III and fibronectin; overexpression of circRNA_33702 was found to exert an inhibitory effect on the expression of the same genes. Mechanistically, circRNA_33702 was demonstrated to bind directly with miR-29b-3p and inhibit its expression. Moreover, WISP1 was identified as a target of miR-29b-3p and the expression of WISP1 was observed to be repressed by miR-29b-3p. Notably, knockdown of circRNA_33702 was found to attenuate the expression of collagen I, collagen III and fibronectin by inhibiting the expression of WISP1, and the observed inhibitory effect can be reversed by miR-29b-3p inhibitor. Finally, inhibition of circRNA_33702 was shown to attenuate interstitial fibrosis in UUO mice via the miR-29b-3p/WISP1 axis. In general, our data show that circRNA_33702 may promote renal fibrosis via the miR-29b-3p/WISP1 axis, which may potentially be developed as a new therapeutic target.

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Section: Resultsmentioning

confidence: 99%

CircRNA_33702 promotes renal fibrosis by targeting the miR-29b-3p/WISP1 pathway

Lee

Wang

2022

Preprint

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“…Several studies reported that circRNAs mediated the progression of diabetic nephropathy, lupus nephritis, and focal segmental glomerulosclerosis [ 8 – 15 ], and only one study demonstrated that circRNA_30032 promoted fibrosis in UUO mice kidney [ 25 ]. In the present study, topological analyses based on the ceRNA network suggested that circRNA_37492 with a homologous hsa_circ_0012138 was the most potential target, considering the fold change and conservation score.…”

Section: Discussionmentioning

confidence: 99%

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

Lee

et al. 2022

Cell Death Dis

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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.

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“…A previous study revealed that AKAP13 was expressed in the alveolar epithelium and lymphoid follicles of patients with idiopathic pulmonary fibrosis, and AKAP13 mRNA expression was higher in lung tissue of patients with IPF than that in lung tissue from controls [ 30 ]. Other studies indicated that circRNA_010383 [ 31 ], circACTR2 [ 32 ], circ_0000064 [ 33 ] and circRNA_30032 [ 34 ] played a key role in renal fibrosis in mice model or cell lines. In this study, we found that hsa_circ_0036649 had a diagnostic value for renal fibrosis.…”

Section: Discussionmentioning

confidence: 99%

Urinary exosomes derived circRNAs as biomarkers for chronic renal fibrosis

Cao

Shi²,

Yang³

et al. 2022

Annals of Medicine

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Background Chronic renal disease (CKD) is a common and irreversible loss of renal function. Renal fibrosis reflected the degree of renal dysfunction. However, the current biomarkers only characterize the renal function instead of indicating the fibrosis degree. The potential diagnostic value of urinary exosomes derived circRNAs for renal fibrosis needs to be further studied. Methods Urine exosomes from 3 chronic kidney disease (CKD) patients without renal fibrosis and 3 renal fibrotic patients were collected and human circRNAs microarray analysis were performed to detect the circRNAs expression profile. 110 biopsy-proven CKD patients and 54 healthy controls were enrolled and urine exosomes derived RNA was isolated. The expression of hsa_circ_0036649 was measured and the correlation with renal function parameter and pathological indicators was performed. The receiver operating characteristic (ROC) curve for the diagnosis of renal fibrosis was calculated. Results Human circRNAs microarray showed 365 circRNAs up expressed and 195 circRNAs down expressed in renal fibrotic patients compared to none fibrosis CKD patients. The expression of hsa_circ_0036649 was decreased in renal fibrotic patients according to RT-PCR and correlated with serum creatinine, blood urea nitrogen (BUN), estimated glomerular filtration rate and cystatin c. Further, the expression of hsa_circ_0036649 was correlated with the score of tubulointerstitial fibrosis (TIF) and the score of glomerular sclerosis. The ROC curve showed that hsa_circ_0036649 may predict renal fibrosis at a cut-off value of 0.597 with a sensitivity of 45.5% and specificity of 87.9%. Conclusion Expression of urinary exosomes derived hsa_circ_0036649 associated with the degree of renal fibrosis. Its potential role as a biomarker in CKD remained to be supported by further follow-up studies. Key Messages circRNAs profile in urine exosomes in renal fibrosis patients was revealed. The expression of urine exosomes derived hsa_circ_0036649 was correlated to renal function and fibrosis degree. circRNAs derived from urinary exosomes may become a new research direction for biomarkers of renal fibrosis.

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CircRNA_30032 promotes renal fibrosis in UUO model mice via miRNA-96-5p/HBEGF/KRAS axis

Cited by 22 publications

References 49 publications

CircRNA_33702 promotes renal fibrosis by targeting the miR-29b-3p/WISP1 pathway

CircRNA_33702 promotes renal fibrosis by targeting the miR-29b-3p/WISP1 pathway

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

Urinary exosomes derived circRNAs as biomarkers for chronic renal fibrosis

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