Seungil Ro
University of Nevada School of Medicine, USA
Title: Loss of miR-10b triggers depletion of interstitial cells of Cajal in diabetic mice
Biography
Biography: Seungil Ro
Abstract
Both acute and chronic hyperglycemia in diabetes are linked to gastrointestinal (GI) complications that can change normal function of motility. One of the common pathological abnormalities in diabetic patients in the GI tract is characterized by depletion of interstitial cells of Cajal (ICCs). ICCs are pacemakers in the GI tract that regulate GI motility through spontaneous electrical slow waves. ICCs exclusively express the receptor tyrosine kinase KIT, which is required for the normal development and maintenance of ICCs. However, underlying molecular mechanisms in depletion of ICCs in diabetic patients are largely elusive. Here we report a microRNA mediated ICC depletion in the diabetic animal model. We identified miR-10b-5p as a diabetic cell marker that was dramatically diminished in the diabetic ICCs. MiR-10b-5p targets an epigenetic repressor, nuclear receptor corepressor 2 (NCOR2), which negatively regulates expression of KIT. Expression of KIT and NCOR2 proteins was negatively related in diabetic intestine where KIT+ ICCs were found in lower concentration. ICC-restricted miR-10b knockout in mice resulted in partial depletion of ICCs in the intestine. Our findings on KIT regulation by miR-10b-5p targeted NCOR2 offer a new insight into how ICCs is phenotypically changed and become non-functional in diabetic conditions. Moreover, this study suggests miR-10b-5p may be potentially an attractive therapeutic target to restore KIT expression in diabetic ICCs of patients with GI dysmotility.