title: miR-204 regulates epithelial-mesenchymal transition by targeting SP1 in the tubular epithelial cells after acute kidney injury induced by ischemia-reperfusion.
abstract: Acute kidney injury (AKI) is a disease where kidney function is lost almost instantaneously; it can develop very rapidly over few hours to maximum of few days. Despite the advent of technology, the clinical management against this disease is very poor, and most of the time it is life-threatening. AKI has been actively regulated by extracellular matrix proteins (ECM), however, its underlying mechanism of regulation during AKI progression is very poorly understood. In this study, we explored the integrated network of mRNA and microRNAs (miRNAs) that maintains the progression of ECM after induction of AKI by lethal ischemia. To identify key regulators of ECM, we screened large number of transcriptomes using laser capture microdissection (LCM) technique in addition to microarray and RT-qPCR. Our result clearly showed that 9 miRNAs including miR-21, miR-483, miR-5115, miR-204e, miR-128, miR-181c, miR-203, miR-204 and miR-204c were highly regulated, out of which miR-204 expression change (decrease) was most drastic during ischemia/reperfusion. Detail mechanistic study utilizing combined experimental and computational approach revealed that TGF-β signaling pathway was potentially modulated by deregulated miRNA-204 through SP1, where the TGF-β signaling pathway plays a vital role in ECM regulation. Apart from targeting SP1 and antagonizing epithelial-mesenchymal transition (EMT) signaling our result also showed that miR-204 protects interstitial tissue of renal tubules from chronic fibrotic change. Altogether our study provides sufficient details of how miRNA mediated ECM regulation occur during AKI, which can be effectively utilized in future for better AKI management and diagnosis.
authors.affiliation: Department of Nephrology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, P.R. China.
authors.forename: Shun-Jie
authors.initials: SJ
authors.lastname: Chen
authors.affiliation: Department of Nephrology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, P.R. China.
authors.forename: Ping
authors.initials: P
authors.lastname: Wu
authors.affiliation: Department of Nephrology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, P.R. China.
authors.forename: Li-Jing
authors.initials: LJ
authors.lastname: Sun
authors.affiliation: Department of Nephrology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, P.R. China.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhou
authors.affiliation: Department of Nephrology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Niu
authors.affiliation: Department of Nephrology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, P.R. China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Nephrology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, P.R. China.
authors.forename: Fu-Jun
authors.initials: FJ
authors.lastname: Lin
authors.affiliation: Department of Nephrology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, P.R. China.
authors.forename: Geng-Ru
authors.initials: GR
authors.lastname: Jiang
mesh_terms: D058186:Acute Kidney Injury / Q000209:etiology / Q000473:pathology*; D000818:Animals; D015536:Down-Regulation; D004847:Epithelial Cells / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005355:Fibrosis / Q000235:genetics / Q000473:pathology; D005786:Gene Expression Regulation; D007684:Kidney Tubules / Q000473:pathology; D061346:Laser Capture Microdissection; D008297:Male; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics*; D015427:Reperfusion Injury / Q000150:complications*; D016329:Sp1 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: C574692:MIRN204 microRNA, mouse; D035683:MicroRNAs; D016329:Sp1 Transcription Factor; D016212:Transforming Growth Factor beta