Activation of the Melanocortin-4 receptor signaling by α-MSH stimulates nerve-dependent mouse digit regeneration
Abstract 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 th...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
SpringerOpen
2021-05-01
|
| Series: | Cell Regeneration |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13619-021-00081-9 |
| _version_ | 1818720685284917248 |
|---|---|
| author | Hanqian Xu Hailin Zhang Yanqing Fang Huiran Yang Ying Chen Chao Zhang Gufa Lin |
| author_facet | Hanqian Xu Hailin Zhang Yanqing Fang Huiran Yang Ying Chen Chao Zhang Gufa Lin |
| author_sort | Hanqian Xu |
| collection | DOAJ |
| description | Abstract 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 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 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. |
| first_indexed | 2024-12-17T20:26:46Z |
| format | Article |
| id | doaj.art-750f783ad5864b7297b84b4fa8fb7378 |
| institution | Directory Open Access Journal |
| issn | 2045-9769 |
| language | English |
| last_indexed | 2024-12-17T20:26:46Z |
| publishDate | 2021-05-01 |
| publisher | SpringerOpen |
| record_format | Article |
| series | Cell Regeneration |
| spelling | doaj.art-750f783ad5864b7297b84b4fa8fb73782022-12-21T21:33:44ZengSpringerOpenCell Regeneration2045-97692021-05-0110111110.1186/s13619-021-00081-9Activation of the Melanocortin-4 receptor signaling by α-MSH stimulates nerve-dependent mouse digit regenerationHanqian Xu0Hailin Zhang1Yanqing Fang2Huiran Yang3Ying Chen4Chao Zhang5Gufa Lin6Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Orthopaedic Department of Tongji Hospital, School of Life Sciences and Technology, Tongji UniversityKey Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Orthopaedic Department of Tongji Hospital, School of Life Sciences and Technology, Tongji UniversityKey Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Orthopaedic Department of Tongji Hospital, School of Life Sciences and Technology, Tongji UniversityKey Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Orthopaedic Department of Tongji Hospital, School of Life Sciences and Technology, Tongji UniversityStem Cell Institute, University of MinnesotaTranslational Medical Center for Stem Cell Therapy and Institute for Regenerative Medicine, Shanghai East Hospital, Shanghai Key Laboratory of Signaling and Disease Research, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji UniversityKey Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Orthopaedic Department of Tongji Hospital, School of Life Sciences and Technology, Tongji UniversityAbstract 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 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 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.https://doi.org/10.1186/s13619-021-00081-9MC4RMc4r-gfpα-MSHDigit regenerationDistalProximal |
| spellingShingle | Hanqian Xu Hailin Zhang Yanqing Fang Huiran Yang Ying Chen Chao Zhang Gufa Lin Activation of the Melanocortin-4 receptor signaling by α-MSH stimulates nerve-dependent mouse digit regeneration Cell Regeneration MC4R Mc4r-gfp α-MSH Digit regeneration Distal Proximal |
| title | Activation of the Melanocortin-4 receptor signaling by α-MSH stimulates nerve-dependent mouse digit regeneration |
| title_full | Activation of the Melanocortin-4 receptor signaling by α-MSH stimulates nerve-dependent mouse digit regeneration |
| title_fullStr | Activation of the Melanocortin-4 receptor signaling by α-MSH stimulates nerve-dependent mouse digit regeneration |
| title_full_unstemmed | Activation of the Melanocortin-4 receptor signaling by α-MSH stimulates nerve-dependent mouse digit regeneration |
| title_short | Activation of the Melanocortin-4 receptor signaling by α-MSH stimulates nerve-dependent mouse digit regeneration |
| title_sort | activation of the melanocortin 4 receptor signaling by α msh stimulates nerve dependent mouse digit regeneration |
| topic | MC4R Mc4r-gfp α-MSH Digit regeneration Distal Proximal |
| url | https://doi.org/10.1186/s13619-021-00081-9 |
| work_keys_str_mv | AT hanqianxu activationofthemelanocortin4receptorsignalingbyamshstimulatesnervedependentmousedigitregeneration AT hailinzhang activationofthemelanocortin4receptorsignalingbyamshstimulatesnervedependentmousedigitregeneration AT yanqingfang activationofthemelanocortin4receptorsignalingbyamshstimulatesnervedependentmousedigitregeneration AT huiranyang activationofthemelanocortin4receptorsignalingbyamshstimulatesnervedependentmousedigitregeneration AT yingchen activationofthemelanocortin4receptorsignalingbyamshstimulatesnervedependentmousedigitregeneration AT chaozhang activationofthemelanocortin4receptorsignalingbyamshstimulatesnervedependentmousedigitregeneration AT gufalin activationofthemelanocortin4receptorsignalingbyamshstimulatesnervedependentmousedigitregeneration |