HypoxamiR-210 accelerates wound healing in diabetic mice by improving cellular metabolism.

Autor: Narayanan S; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.; Department of Endocrinology and Diabetes, Karolinska University Hospital, Stockholm, Sweden., Eliasson Angelstig S; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.; Department of Endocrinology and Diabetes, Karolinska University Hospital, Stockholm, Sweden., Xu C; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.; Department of Endocrinology and Diabetes, Karolinska University Hospital, Stockholm, Sweden., Grünler J; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.; Department of Endocrinology and Diabetes, Karolinska University Hospital, Stockholm, Sweden., Zhao A; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden., Zhu W; Department of Nosocomial Infection Control, China Medical University, Shenyang, China., Xu Landén N; Dermatology and Venereology division, Department of Medicine Solna, Center for Molecular Medicine and Ming Wai Lau Centre for Reparative Medicine, Karolinska Institutet, Stockholm, Sweden., Ståhle M; Dermatology and Venereology division, Department of Medicine Solna, Center for Molecular Medicine and Ming Wai Lau Centre for Reparative Medicine, Karolinska Institutet, Stockholm, Sweden., Zhang J; Department of Infectious Disease, China Medical University, Shenyang, China., Ivan M; Departments of Medicine, Microbiology and Immunology, Indiana University, Indianapolis, IN, USA., Maltesen RG; Department of Anesthesia and Intensive Care Medicine, Aalborg University Hospital, Aalborg, Denmark., Botusan IR; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.; Department of Endocrinology and Diabetes, Karolinska University Hospital, Stockholm, Sweden., Rajamand Ekberg N; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.; Department of Endocrinology and Diabetes, Karolinska University Hospital, Stockholm, Sweden., Zheng X; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden. Xiaowei.zheng@ki.se.; Department of Endocrinology and Diabetes, Karolinska University Hospital, Stockholm, Sweden. Xiaowei.zheng@ki.se., Catrina SB; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden. Sergiu-Bogdan.Catrina@ki.se.; Department of Endocrinology and Diabetes, Karolinska University Hospital, Stockholm, Sweden. Sergiu-Bogdan.Catrina@ki.se.; Center for Diabetes, Academic Specialist Centrum, Stockholm, Sweden. Sergiu-Bogdan.Catrina@ki.se.
Jazyk: angličtina
Zdroj: Communications biology [Commun Biol] 2020 Dec 14; Vol. 3 (1), pp. 768. Date of Electronic Publication: 2020 Dec 14.
DOI: 10.1038/s42003-020-01495-y
Abstrakt: 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.
Databáze: MEDLINE
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