TY - JOUR
T1 - HypoxamiR-210 accelerates wound healing in diabetic mice by improving cellular metabolism
AU - Narayanan, Sampath
AU - Eliasson Angelstig, Sofie
AU - Xu, Cheng
AU - Grünler, Jacob
AU - Zhao, Allan
AU - Zhu, Wan
AU - Xu Landén, Ning
AU - Ståhle, Mona
AU - Zhang, Jingping
AU - Ivan, Mircea
AU - Maltesen, Raluca Georgiana
AU - Botusan, Ileana Ruxandra
AU - Rajamand Ekberg, Neda
AU - Zheng, Xiaowei
AU - Catrina, Sergiu-Bogdan
PY - 2020/12/14
Y1 - 2020/12/14
N2 - Wound healing is a high energy demanding process that needs a good coordination of the mitochondria with glycolysis in the characteristic highly hypoxic environment. In diabetes, hyperglycemia impairs the adaptive responses to hypoxia with profound negative effects on different cellular compartments of wound healing. miR-210 is a hypoxia-induced microRNA that regulates cellular metabolism and processes important for wound healing. Here, we show that hyperglycemia blunted the hypoxia-dependent induction of miR-210 both in vitro and in human and mouse diabetic wounds. The impaired regulation of miR-210 in diabetic wounds is pathogenic, since local miR-210 administration accelerated wound healing specifically in diabetic but not in non-diabetic mice. miR-210 reconstitution restores the metabolic balance in diabetic wounds by reducing oxygen consumption rate and ROS production and by activating glycolysis with positive consequences on cellular migration. In conclusion, miR-210 accelerates wound healing specifically in diabetes through improvement of the cellular metabolism.
AB - Wound healing is a high energy demanding process that needs a good coordination of the mitochondria with glycolysis in the characteristic highly hypoxic environment. In diabetes, hyperglycemia impairs the adaptive responses to hypoxia with profound negative effects on different cellular compartments of wound healing. miR-210 is a hypoxia-induced microRNA that regulates cellular metabolism and processes important for wound healing. Here, we show that hyperglycemia blunted the hypoxia-dependent induction of miR-210 both in vitro and in human and mouse diabetic wounds. The impaired regulation of miR-210 in diabetic wounds is pathogenic, since local miR-210 administration accelerated wound healing specifically in diabetic but not in non-diabetic mice. miR-210 reconstitution restores the metabolic balance in diabetic wounds by reducing oxygen consumption rate and ROS production and by activating glycolysis with positive consequences on cellular migration. In conclusion, miR-210 accelerates wound healing specifically in diabetes through improvement of the cellular metabolism.
U2 - 10.1038/s42003-020-01495-y
DO - 10.1038/s42003-020-01495-y
M3 - Journal article
C2 - 33318569
SN - 2399-3642
VL - 3
JO - Communications Biology
JF - Communications Biology
IS - 1
M1 - 768
ER -