Non-coding RNA research
circHIPK3 promotes pro-fibrotic epithelial reprogramming via the miR-29a-3p/SPARC axis with associated enhancement of TGF-β/SMAD signaling
By Zhou Y, Huang Y, Ma J and 5 others.
Abstract
Background
Idiopathic pulmonary fibrosis (IPF) is fatal with limited treatments. circHIPK3 is upregulated in fibrotic lungs, but its role in lung epithelial cells and connection to TGF-β/SMAD signaling are unclear.
Methods
We used TGF-β1-stimulated lung epithelial cells (A549, BEAS-2B) and a bleomycin-induced mouse model. circHIPK3 was silenced with ASOs. Direct interactions were assessed using luciferase reporter and RNA pull-down assays, and functional intervention experiments were performed to investigate the proposed regulatory axis. TGF-β/SMAD activity was measured by CAGA reporter, and SPARC-TGFBR2 association by co-IP/colocalization.
