[HTML][HTML] Long non-coding RNA RNF7 promotes the cardiac fibrosis in rat model via miR-543/THBS1 axis and TGFβ1 activation

F Ouyang, X Liu, G Liu, H Qiu, Y He, H Hu… - Aging (Albany NY …, 2020 - ncbi.nlm.nih.gov
F Ouyang, X Liu, G Liu, H Qiu, Y He, H Hu, P Jiang
Aging (Albany NY), 2020ncbi.nlm.nih.gov
Cardiac fibrosis (CF) is regulated by multiple factors, including transforming growth factor β1
(TGFβ1) and non-coding RNAs. Thrombospondin 1 (TSP1) is a physiologic regulator of
TGFβ activation. Here, we performed microarray analyses on mRNAs and lncRNAs
differentially-expressed in the CF and normal rat hearts. KEGG signaling annotation and GO
enrichment analyses were performed to validate the roles of extracellular matrix (ECM) and
TSP1-enhanced TGFβ activation in CF. The co-expression network between differentially …
Abstract
Cardiac fibrosis (CF) is regulated by multiple factors, including transforming growth factor β1 (TGFβ1) and non-coding RNAs. Thrombospondin 1 (TSP1) is a physiologic regulator of TGFβ activation. Here, we performed microarray analyses on mRNAs and lncRNAs differentially-expressed in the CF and normal rat hearts. KEGG signaling annotation and GO enrichment analyses were performed to validate the roles of extracellular matrix (ECM) and TSP1-enhanced TGFβ activation in CF. The co-expression network between differentially-expressed lncRNAs and ECM-related factors was constructed to identify candidate lncRNAs and miRNAs. We found that lncRNA Homo sapiens ring finger protein 7 (lnc RNF7) was significantly correlated with TSP1 and ECM. Lnc RNF7 silence could attenuate isoproterenol (ISP)-induced CF in rat heart in vivo and in rat cardiac fibroblasts in vitro. Moreover, angiotensin II (Ang II)-induced CF in rat cardiac fibroblasts could also be attenuated by Lnc RNF7 silence. Furthermore, miR-543 could simultaneously target lnc RNF7 and 3'UTR of TSP1. Lnc RNF7 silence suppressed, while miR-543 inhibition promoted TSP1 protein and TGFβ activation, as well as ECM markers expression. The effects of lnc RNF7 silence was significantly reversed by miR-543 inhibition. In conclusion, CF progression might be regulated by lnc RNF7/miR-543 axis via TSP1-mediated TGFβ activation.
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