Genome-wide transcriptional analysis of differentially expressed genes in diabetic, healing corneal epithelial cells: hyperglycemia-suppressed TGF?3 expression contributes to the delay of epithelial wound healing in diabetic corneas.

ABSTRACT: 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 TGF?3 therein. Genome-wide cDNA microarray analysis revealed 1,888 differentially expressed genes in the healing epithelia of normal (NL) versus type 1 DM rat corneas. Gene ontology and enrichment analyses indicated TGF? signaling as a major altered pathway. Among three TGF? isoforms, TGF-?1 and ?3 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 TGF-?3 contributed to wound healing in NL corneas. Moreover, exogenously added TGF-?3 accelerated epithelial wound closure in type 2 rat and type 1 mouse DM corneas via Smad and PI3K-AKT signaling pathways, autoregulation, and/or upregulation of Serpine1, a well-known TGF? target gene. Taken together, our study for the first time provides a comprehensive list of genes differentially expressed in the healing CECs of NL versus diabetic corneas and suggests the therapeutic potential of TGF-?3 for treating corneal and skin wounds in diabetic patients.

SUBMITTER: Bettahi I 

PROVIDER: S-EPMC3900551 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature