Loss of ARNT in skeletal muscle limits muscle regeneration in aging.

Autor: Endo Y; Division of Plastic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Baldino K; Division of Plastic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Li B; Division of Plastic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.; Department of Plastic and Aesthetic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China., Zhang Y; Division of Plastic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.; Department of Plastic and Aesthetic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China., Sakthivel D; Division of Human Genetics, Baylor College of Medicine, Houston, TX, USA., MacArthur M; Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, MA, USA.; Division of Vascular and Endovascular Surgery, Brigham and Women's Hospital, Boston, MA, USA., Panayi AC; Division of Plastic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Kip P; Division of Vascular and Endovascular Surgery, Brigham and Women's Hospital, Boston, MA, USA., Spencer DJ; Division of Endocrinology, Brigham and Women's Hospital, Boston, MA, USA., Jasuja R; Division of Endocrinology, Brigham and Women's Hospital, Boston, MA, USA., Bagchi D; Department of Orthopedic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Bhasin S; Division of Endocrinology, Brigham and Women's Hospital, Boston, MA, USA., Nuutila K; Division of Plastic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Neppl RL; Department of Orthopedic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Wagers AJ; Joslin Diabetes Center, Boston, MA, USA.; Harvard Department of Stem Cell and Regenerative Biology, Harvard Stem Cell Institute, Cambridge, MA, USA.; Paul F. Glenn Center for the Biology of Aging, Harvard Medical School, Boston, MA, USA., Sinha I; Division of Plastic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.; Harvard Department of Stem Cell and Regenerative Biology, Harvard Stem Cell Institute, Cambridge, MA, USA.
Jazyk: angličtina
Zdroj: FASEB journal : official publication of the Federation of American Societies for Experimental Biology [FASEB J] 2020 Dec; Vol. 34 (12), pp. 16086-16104. Date of Electronic Publication: 2020 Oct 08.
DOI: 10.1096/fj.202000761RR
Abstrakt: The ability of skeletal muscle to regenerate declines significantly with aging. The expression of aryl hydrocarbon receptor nuclear translocator (ARNT), a critical component of the hypoxia signaling pathway, was less abundant in skeletal muscle of old (23-25 months old) mice. This loss of ARNT was associated with decreased levels of Notch1 intracellular domain (N1ICD) and impaired regenerative response to injury in comparison to young (2-3 months old) mice. Knockdown of ARNT in a primary muscle cell line impaired differentiation in vitro. Skeletal muscle-specific ARNT deletion in young mice resulted in decreased levels of whole muscle N1ICD and limited muscle regeneration. Administration of a systemic hypoxia pathway activator (ML228), which simulates the actions of ARNT, rescued skeletal muscle regeneration in both old and ARNT-deleted mice. These results suggest that the loss of ARNT in skeletal muscle is partially responsible for diminished myogenic potential in aging and activation of hypoxia signaling holds promise for rescuing regenerative activity in old muscle.
(© 2020 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.)
Databáze: MEDLINE
Externí odkaz: