CCN2/CTGF increases expression of miR-302 microRNAs, which target the TGF beta type II receptor with implications for nephropathic cell phenotypes

Signalling interplay between transforming growth factor-beta (TGF beta) and CCN2 [also called connective tissue growth factor (CTGF)] plays a crucial role in the progression of diabetic nephropathy and has been implicated in cellular differentiation. To investigate the potential role of microRNAs (miRNAs) in the mediation of this signalling network, we performed miRNA screening in mesangial cells treated with recombinant human CCN2. Analysis revealed a cohort of 22 miRNAs differentially expressed by twofold or more, including members of the miR-302 family. Target analysis of miRNA to 3'-untranslated regions (3'-UTRs) identified TGF beta receptor II (T beta RII) as a potential miR-302 target. In mesangial cells, decreased T beta RII expression was confirmed in response to CCN2 together with increased expression of miR-302d. T beta RII was confirmed as an miR-302 target, and inhibition of miR-302d was sufficient to attenuate the effect of CCN2 on T beta RII. Data from the European Renal cDNA Biopsy Bank revealed decreased T beta RII in diabetic patients, suggesting pathophysiological significance. In a mouse model of fibrosis (UUO), miR-302d was increased, with decreased T beta RII expression and aberrant signalling, suggesting relevance in chronic fibrosis. miR-302d decreased TGF beta-induced epithelial mesenchymal transition (EMT) in renal HKC8 epithelial cells and attenuated TGF beta-induced mesangial production of fibronectin and thrombospondin. In summary, we demonstrate a new mode of regulation of TGF beta by CCN2, and conclude that the miR-302 family has a role in regulating growth factor signalling pathways, with implications for nephropathic cell fate transitions.

Si j'étais roi !... : opéra-comique en trois actes et quatre tableaux. [Suivi de] La dame aux jambes d'azur : pochade en un acte. Livr. 302 / par MM. Dennery et Brésil ; musique de M. Adolphe Adam...par MM. Marc-Michel et E. Labiche

Collection : Théâtre contemporain illustré ; 301e et 302e livraisons

Jornal da UNESP, 2014, ano XXVIII, n. 302

Jornal elaborado pela Assessoria de Comunicação e Imprensa da Reitoria da UNESP

Glossaire hébreu-francais du XIII. siècle : recueil de mots hébreux bibliques avec trad. francaise ; Ms. de la Bibliotheque Nationale, fonds hébreu, no. 302

publié sous les auspices de l'Académie des Inscriptions et Belles-Lettres par Mayer Lambert et Louis Brandin