Muscle satellite cells are impaired in type 2 diabetic mice by elevated extracellular adenosine
Research output: Journal Publications and Reviews (RGC: 21, 22, 62) › 21_Publication in refereed journal › peer-review
Author(s)
Related Research Unit(s)
Detail(s)
Original language | English |
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Article number | 110884 |
Journal / Publication | Cell Reports |
Volume | 39 |
Issue number | 9 |
Online published | 31 May 2022 |
Publication status | Published - 31 May 2022 |
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DOI | DOI |
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Attachment(s) | Documents
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Link to Scopus | https://www.scopus.com/record/display.uri?eid=2-s2.0-85131120129&origin=recordpage |
Permanent Link | https://scholars.cityu.edu.hk/en/publications/publication(9299c673-03bf-409e-9266-31bf5b35196c).html |
Abstract
Muscle regeneration is known to be defective under diabetic conditions. However, the underlying mechanisms remain less clear. Adult quiescent muscle satellite cells (MuSCs) from leptin-receptor-deficient (i.e., db/db) diabetic mice are defective in early activation in vivo, but not in culture, suggesting the involvement of pathogenic niche factors. Elevated extracellular adenosine (eAdo) and AMP (eAMP) are detected under diabetic conditions. eAdo and eAMP potently inhibit cell cycle re-entry of quiescent MuSCs and injury-induced muscle regeneration. Mechanistically, eAdo and eAMP engage the equilibrative Ado transporters (ENTs)-Ado kinase (ADK)-AMPK signaling axis in MuSCs to inhibit the mTORC1-dependent cell growth checkpoint. eAdo and eAMP also inhibit early activation of quiescent fibroadipogenic progenitors and human MuSCs by the same mechanism. Treatment of db/db diabetic mice with an ADK inhibitor partially rescues the activation defects of MuSCs in vivo. Thus, both ADK and ENTs represent potential therapeutic targets for restoring the regenerative functions of tissue stem cells in patients with diabetes.
Research Area(s)
- adenosine kinase (ADK), AMPK, CP: Metabolism, diabetes, equilibrative nucleoside transporter (ENT), extracellular adenosine, extracellular AMP, mTORC1, muscle satellite cells (MuSCs)
Bibliographic Note
Citation Format(s)
In: Cell Reports, Vol. 39, No. 9, 110884, 31.05.2022.
Research output: Journal Publications and Reviews (RGC: 21, 22, 62) › 21_Publication in refereed journal › peer-review