RGD Reference Report - Impaired Epithelial Wound Healing and EGFR Signaling Pathways in the Corneas of Diabetic Rats. - Rat Genome Database

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Impaired Epithelial Wound Healing and EGFR Signaling Pathways in the Corneas of Diabetic Rats.

Authors: Xu, K  Yu, FS 
Citation: Xu K and Yu FS, Invest Ophthalmol Vis Sci. 2011 Feb 17.
RGD ID: 5131482
Pubmed: PMID:21330660   (View Abstract at PubMed)
PMCID: PMC3109029   (View Article at PubMed Central)
DOI: DOI:10.1167/iovs.10-5670   (Journal Full-text)

Purpose. The aim of the study was to investigate the effects of hyperglycemia on EGFR-mediated wound response and -signal transduction in the corneal epithelium of type I diabetes mellitus (DM) rats. Methods. Corneal epithelia were removed from STZ- and weight-matched normal rats. Wound healing was monitored by fluorescein staining at 24h or 48h post epithelial debridement. Phosphorylation of EGFR, AKT, ERK and BAD was determined by Western blotting. The distribution of phospho-AKT and proliferating cell nuclear antigen (PCNA) in rat corneas was examined by immunohistochemistry. Cell death was evaluated by TUNEL staining. Results. A significant delay in corneal epithelial wound healing was observed 48h post wounding in diabetic compared with the weight-matched control rats. In DM rat corneas, epithelial cells demonstrated diminished responses to wounding as assessed by the phosphorylation of EGFR and its downstream signaling molecules AKT and ERK. Furthermore, while the distribution pattern of phospho-AKT suggested a role for AKT in epithelial migration and proliferation in normoglycemic rat corneas, it was abrogated in the healing epithelia of DM rats. Consistent with impaired AKT activity, the number of PCNA staining cells was also greatly reduced in the healing corneas of diabetic rats. Finally, decreases in pBAD (Ser(136), Ser(112)) and increases in TUNEL positive cells were observed in both uninjured and healing corneal epithelia of DM, but not in the control rats. Conclusions. In the corneas of SZT rats, EGFR-PI3K-AKT and -ERK as well as their downstream BAD signaling pathways in migratory epithelium were altered, resulting in increased apoptosis, decreased cell proliferation, and delayed wound closure.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Experimental Diabetes Mellitus  ISOAkt1 (Rattus norvegicus)5131482; 5131482protein:decreased serine phosphorylation:corneaRGD 
Experimental Diabetes Mellitus  IDA 5131482; 5131482protein:decreased serine phosphorylation:corneaRGD 
Experimental Diabetes Mellitus  ISOBad (Rattus norvegicus)5131482; 5131482protein:decreased serine phosphorylation:corneaRGD 
Experimental Diabetes Mellitus  ISOEgfr (Rattus norvegicus)5131482; 5131482protein:decreased tyrosine phosphorylation:corneal epithelial cell (rat)RGD 
Experimental Diabetes Mellitus  IDA 5131482protein:decreased tyrosine phosphorylation:corneaRGD 
Experimental Diabetes Mellitus  ISOMapk1 (Rattus norvegicus)5131482; 5131482protein:decreased phosphorylation:corneaRGD 
Experimental Diabetes Mellitus  ISOMapk3 (Rattus norvegicus)5131482; 5131482protein:decreased phosphorylation:corneaRGD 
Experimental Diabetes Mellitus  IDA 5131482; 5131482protein:decreased phosphorylation:corneaRGD 

Objects Annotated

Genes (Rattus norvegicus)
Akt1  (AKT serine/threonine kinase 1)
Bad  (BCL2-associated agonist of cell death)
Egfr  (epidermal growth factor receptor)
Mapk1  (mitogen activated protein kinase 1)
Mapk3  (mitogen activated protein kinase 3)

Genes (Mus musculus)
Akt1  (thymoma viral proto-oncogene 1)
Bad  (BCL2-associated agonist of cell death)
Egfr  (epidermal growth factor receptor)
Mapk1  (mitogen-activated protein kinase 1)
Mapk3  (mitogen-activated protein kinase 3)

Genes (Homo sapiens)
AKT1  (AKT serine/threonine kinase 1)
BAD  (BCL2 associated agonist of cell death)
EGFR  (epidermal growth factor receptor)
MAPK1  (mitogen-activated protein kinase 1)
MAPK3  (mitogen-activated protein kinase 3)


Additional Information