HGFA is an injury-regulated systemic factor that induces the transition of stem cells into GAlert
Open accessAbstract
The activation of quiescent stem cells into the cell cycle is a key step in initiating the process of tissue repair. We recently reported that quiescent stem cells can transition into G Alert , a cellular state in which they have an increased functional ability to activate and participate in tissue repair. However, the precise molecular signals that induce G Alert in stem cells have remained elusive. Here, we show that the injury-induced regulation of hepatocyte growth factor (HGF) proteolytic processing via the systemic protease, hepatocyte growth factor activator (HGFA), stimulates G Alert in skeletal muscle stem cells (MuSCs) and fibro-adipogenic progenitors (FAPs). We demonstrate that administering active HGFA to animals is sufficient to induce G Alert in stem cells throughout the body and to significantly accelerate the processes of stem cell activation and tissue repair. Our data suggest that factors that induce G Alert will have broad therapeutic applications for regenerative medicine and wound healing.
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Priming of activation by systemic signaling factors improves regeneration.
“Likewise, ‘priming’ of activation by systemic signaling factors has been reported to improve regeneration (Rodgers et al., 2014, 2017).”
From Aging induces aberrant state transition kinetics in murine muscle stem cells (2020) · cites this paper as Rodgers et al., 2017
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- Authors
- Rodgers, J. T., Schroeder, M. D., Ma, C., & Rando, T. A.
- Affiliations
- Stanford Medicine (US)
- VA Palo Alto Health Care System (US)
- Corresponding author
- Rodgers, Joseph T.
- Rando, Thomas A.
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2017-04
- Volume
- 19
- Issue
- 3
- Pages
- 479-486
- ISSN
- 2211-1247 (ISSN-L)
- PMC
- PMC5468096
- OpenAlex
- W2606992329
- Cited by
- 161
- References
- 30
- Citations by year
- 2026: 6 · 2025: 13 · 2024: 27 · 2023: 18 · 2022: 20 · 2021: 13 · 2020: 25 · 2019: 16 · 2018: 16 · 2017: 7
- FWCI
- 7.15
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- U.S. Department of Veterans Affairs (I01BX002324)
- Glenn Foundation for Medical Research (P01 AG036695, R01 AR062185)
- Genentech
- Donald E. and Delia B. Baxter Foundation
- National Institutes of Health (AG041764)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
- Keywords
- hepatocyte growth factor activator, hepatocyte growth factor, quiescent stem cells, skeletal muscle stem cells, fibro-adipogenic progenitors, tissue repair, injury response, protease activation, stem cell activation, wound healing, regenerative medicine
- MeSH terms
- Animals, Cell Cycle, Fibroblasts, Kinetics, Mice, Inbred C57BL, Serine Endopeptidases, Stem Cells, Wound Healing, Adipocytes, Mice, Knockout, Muscle, Skeletal, Serum, Adipogenesis
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