Sonic hedgehog improves ischemia-induced neovascularization by enhancing endothelial progenitor cell function in type 1 diabetes

Molecular and Cellular Endocrinology
Yuan QinJian-Dong Luo

Abstract

The Sonic hedgehog (Shh) pathway is downregulated in type 1 diabetes, and it has been reported that augmentation of this pathway may alleviate diabetic complications. However, the cellular mechanisms underlying these protective effects are poorly understood. Recent studies indicate that impaired function of endothelial progenitor cells (EPCs) may contribute to cardiovascular problems in diabetes. We hypothesized that impaired Shh signaling contribute to endothelial progenitor cell dysfunction and that activating the Shh signaling pathway may rescue EPC function and promote diabetic neovascularization. Adult male C57/B6 mice and streptozotocin (STZ)-induced type 1 diabetic mice were used. Gli1 and Ptc1 protein levels were reduced in EPCs from diabetic mice, indicating inhibition of the Shh signaling pathway. EPC migration, tube formation ability, and mobilization were impaired in diabetic mice compared with non-diabetic controls (p < 0.05 vs control), and all were improved by in vivo administration of the Shh pathway receptor agonist SAG (p < 0.05 vs diabetes). SAG significantly increased capillary density and blood perfusion in the ischemic hindlimbs of diabetic mice (p < 0.05 vs diabetes). The AKT activity was lower in EPCs fr...Continue Reading

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Citations

May 20, 2017·Cellular and Molecular Life Sciences : CMLS·Marina Dunaeva, Johannes Waltenberger
Dec 14, 2018·International Journal of Molecular Sciences·Igor GiarrettaRoberto Pola
Oct 28, 2019·International Journal of Molecular Sciences·Igor GiarrettaRoberto Pola
May 13, 2020·BMC Complementary Medicine and Therapies·Yilang LiNing Hou
Jun 27, 2019·International Journal of Molecular Sciences·Candice ChapoulyMarie-Ange Renault
Jan 1, 2021·Archives of Biochemistry and Biophysics·Khaled BenchoulaEng Hwa Wong

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