p38-MAPK pathway is activated in retinopathy of microvascular disease of STZ-induced diabetic rat model

OBJECTIVE: To investigate the role of corticotropin releasing hormone (CRH) in diabetic retinopathy of microvascular disease and the potential mechanism.

MATERIALS AND METHODS: The diabetic rat model was constructed by a single intraperitoneal injection of streptozotocin (STZ). The expression of CRH in the retina of diabetic rats and wild-type rats was detected by Real-Time Polymerase Chain Reaction (RT-PCR). CRH shRNA or Scr shRNA adenovirus was injected into the eyes of diabetic rats and wild-type rats, respectively. The effect of down-regulated CRH on visual electrophysiology in rats was evaluated. Protein expressions of vascular endothelial growth factor (VEGF) and inflammatory factors that were related to the microvascular lesion after CRH downregulation were detected by Western blot. Furthermore, p38 expression was detected by Western blot to explore whether mitogen-activated protein kinase (MAPK) signaling pathway was involved in the function of retinal endothelial cells regulated by CRH.

RESULTS: The expression of CRH was significantly up-regulated in the retina of diabetic rats. RT-PCR results showed that the mRNA level of CRH in the retina of diabetic rats injected with CRH shRNA was decreased. However, no significant change in CRH level was observed in rats injected with Scr shRNA adenovirus. The down-regulated CRH could improve the diabetes-induced visual impairment and retinal inflammatory response. Moreover, the down-regulated CRH led to a decreased phosphorylation level of p38.

CONCLUSIONS: CRH improves the diabetic retinopathy of microvascular disease via the p38-MAPK pathway, which is expected to be a new target for the treatment of diabetic microangiopathy.

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