Authors:
Ilham Bettahi, Haijing Sun, Nan Gao, Feng Wang, Xiaofan Mi, Weiping Chen, Zuguo Liu, and Fu-Shin Yu
Summary:
Patients with diabetes mellitus (DM) may develop corneal complications and delayed wound healing. The aims of this study are to characterize the molecular signatures and biological pathways leading to delayed epithelial wound healing and to delineate the involvement of TGFβ3 therein. Genome-wide cDNA microarray analysis revealed 1888 differentially expressed genes in the healing epithelia of normal (NL) versus type 1 DM rat corneas. Gene Ontology and Enrichment analyses indicated TGFβ-signaling as a major altered pathway. Among three TGFβ isoforms, TGFβ1 and β3 were upregulated in response to wounding in NL corneal epithelial cells (CECs) whereas the latter was greatly suppressed by hyperglycemia in rat type 1 and 2 and mouse type 1 DM models. Functional analysis indicated that TGFβ3 contributed to wound healing in NL corneas. Moreover, exogenously-added TGFβ3 accelerated epithelial wound closure in type 2 rat and type 1 mouse DM corneas via Smad and PI3K-AKT signaling pathways, auto-regulation, and/or upregulation of a well-known TGFβ target gene, Serpine1. Taken together, our study for the first time provides a comprehensive list of genes differentially expressed in the healing CECs of normal versus diabetic corneas and suggests the therapeutic potential of TGFβ3 for treating corneal and skin wounds in diabetic patients.
Source:
Diabetes; (12/04/13)