Activation of the Melanocortin-4 receptor signaling by α-MSH stimulates nerve-dependent mouse digit regeneration.
Denervation
Digit regeneration
Distal
MC4R
Mc4r-gfp
Neurotrophic function
Proximal
α-MSH
Journal
Cell regeneration (London, England)
ISSN: 2045-9769
Titre abrégé: Cell Regen
Pays: China
ID NLM: 101627311
Informations de publication
Date de publication:
03 May 2021
03 May 2021
Historique:
received:
01
02
2021
accepted:
15
03
2021
entrez:
3
5
2021
pubmed:
4
5
2021
medline:
4
5
2021
Statut:
epublish
Résumé
Expression of Mc4r in peripheral organs indicates it has broader roles in organ homeostasis and regeneration. However, the expression and function of Mc4r in the mouse limb and digit has not been fully investigated. Our previous work showed that Mc4r-/- mice fail to regenerate the digit, but whether activation of MC4R signaling could rescue digit regeneration, or stimulate proximal digit regeneration is not clear. We analyzed the expression dynamics of Mc4r in the embryonic and postnatal mouse limb and digit using the Mc4r-gfp mice. We found that Mc4r-GFP is mainly expressed in the limb nerves, and in the limb muscles that are undergoing secondary myogenesis. Expression of Mc4r-GFP in the adult mouse digit is restricted to the nail matrix. We also examined the effect of α-MSH on mouse digit regeneration. We found that administration of α-MSH in the Mc4r+/- mice rescue the delayed regeneration of distal digit tip. α-MSH could rescue distal digit regeneration in denervated hindlimbs. In addition, α-MSH could stimulate regeneration of the proximally amputated digit, which is non-regenerative. Mc4r expression in the mouse limb and digit is closely related to nerve tissues, and α-MSH/MC4R signaling has a neurotrophic role in mouse digit tip regeneration.
Sections du résumé
BACKGROUND
BACKGROUND
Expression of Mc4r in peripheral organs indicates it has broader roles in organ homeostasis and regeneration. However, the expression and function of Mc4r in the mouse limb and digit has not been fully investigated. Our previous work showed that Mc4r-/- mice fail to regenerate the digit, but whether activation of MC4R signaling could rescue digit regeneration, or stimulate proximal digit regeneration is not clear.
RESULTS
RESULTS
We analyzed the expression dynamics of Mc4r in the embryonic and postnatal mouse limb and digit using the Mc4r-gfp mice. We found that Mc4r-GFP is mainly expressed in the limb nerves, and in the limb muscles that are undergoing secondary myogenesis. Expression of Mc4r-GFP in the adult mouse digit is restricted to the nail matrix. We also examined the effect of α-MSH on mouse digit regeneration. We found that administration of α-MSH in the Mc4r+/- mice rescue the delayed regeneration of distal digit tip. α-MSH could rescue distal digit regeneration in denervated hindlimbs. In addition, α-MSH could stimulate regeneration of the proximally amputated digit, which is non-regenerative.
CONCLUSIONS
CONCLUSIONS
Mc4r expression in the mouse limb and digit is closely related to nerve tissues, and α-MSH/MC4R signaling has a neurotrophic role in mouse digit tip regeneration.
Identifiants
pubmed: 33937937
doi: 10.1186/s13619-021-00081-9
pii: 10.1186/s13619-021-00081-9
pmc: PMC8089069
doi:
Types de publication
Journal Article
Langues
eng
Pagination
19Subventions
Organisme : National Natural Science Foundation of China
ID : 31771608
Organisme : National Natural Science Foundation of China
ID : 31771283
Organisme : National Institute of Child Health and Human Development
ID : R01HD084440
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