Aberrant expression of long noncoding RNA (lncRNA) H19 and microRNA (miR)-29b has been implicated in the complications of diabetes mellitus (DM). As a common and important complication of DM, diabetic foot ulcer (DFU) is characterized by high incidence and poor prognosis. Herein, we explored the role of lncRNA H19 in wound healing of DFU. Differentially expressed DM-related lncRNAs were initially screened by microarray data analysis. DFU models were then induced in DM mouse models. The functional role and interaction of lncRNA H19, miR-29b and FBN1 in DFU were subsequently determined by examining the proliferation, migration, and apoptosis of fibroblasts after silencing H19, inhibiting or overexpressing miR-29b and FBN1. According to microarray-based analysis, lncRNA H19 was upregulated in DM. In the ulcerative edge tissues of DFU, high expression of lncRNA H19 and FBN1 and low expression of miR-29b were observed. FBN1 was identified to be a target gene of miR-29b. LncRNA H19 could competitively bind to miR-29b, and then, inhibited its expression, which consequently upregulating FBN1. Silencing of lncRNA H19 led to inhibited proliferation, migration, and enhanced apoptosis of fibroblasts, accompanied by downregulated FBN1 but upregulated miR-29b, which diminished the expression of TGF-β1, Smad3, FN, and Col-1 and reduced extracellular matrix accumulation. Altogether, upregulation of lncRNA H19 can elevate the expression of FBN1 through competitively binding to miR-29b, which enhances the proliferation, migration, and inhibits apoptosis of fibroblasts, thus facilitating the wound healing of DFU.
Keywords: apoptosis; diabetic foot ulcer; fibrillin 1; long noncoding RNA H19; microRNA-29b; proliferation; wound healing.
© 2020 Federation of American Societies for Experimental Biology.