Calcitonin gene-related peptide in diabetic wound repair: efferocytosis, inflammatory resolution, and host defense
4 affiliations
- 1Experimental Research Center, China Academy of Chinese Medical Sciences
- 2College of Physical Education, Yangzhou University, Jiangsu
- 3Beijing Hospital of Traditional Chinese Medicine, Capital Medical University
- 4Shunyi Hospital of Beijing Hospital of Traditional Chinese Medicine
Abstract
Diabetic wounds are characterized by persistent inflammation and impaired tissue repair, with sensory neuropathy potentially disrupting the signals that coordinate these processes. Calcitonin gene-related peptide (CGRP) has emerged as a mediator connecting sensory neurons to myeloid-cell behavior. Experimental studies show that CGRP signaling through the calcitonin receptor-like receptor and receptor activity-modifying protein 1 regulates inflammatory-cell recruitment and macrophage efferocytosis, partly through thrombospondin-1. These findings extend the proposed contribution of sensory nerves beyond protection from injury to active regulation of inflammatory resolution. However, diabetes also compromises the recognition and processing of apoptotic cells, raising the possibility that ligand supplementation alone may not restore clearance. Moreover, CGRP can impair antibacterial defense in some infection models while supporting cutaneous antifungal immunity, and thrombospondin-1 has vascular effects that differ from its clearance-promoting activities. This Mini Review critically integrates these findings with recent CGRP delivery studies, distinguishing evidence from human tissue, diabetic wound models, acute injury, and infection. We argue that therapeutic development should address both neuronal signal availability and recipient-cell competence, while evaluating microbial control and perfusion alongside repair. Local CGRP delivery is a promising preclinical strategy, but its mechanisms and therapeutic window require validation in the heterogeneous environment of human diabetic foot ulcers.
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BibTeX
@article{xie2026calcitonin,
title = {{Calcitonin gene-related peptide in diabetic wound repair: efferocytosis, inflammatory resolution, and host defense}},
author = {Jiding Xie and Lei Shi and ShiDong An and Leiyong Wang and Jingang Dai},
journal = {Frontiers in Endocrinology},
year = {2026},
month = nov,
doi = {10.3389/fendo.2026.2017813},
url = {https://www.frontiersin.org/articles/10.3389/fendo.2026.2017813/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Calcitonin gene-related peptide in diabetic wound repair: efferocytosis, inflammatory resolution, and host defense
AU - Jiding Xie
AU - Lei Shi
AU - ShiDong An
AU - Leiyong Wang
AU - Jingang Dai
PY - 2026
DA - 2026/11/02
JO - Frontiers in Endocrinology
DO - 10.3389/fendo.2026.2017813
UR - https://www.frontiersin.org/articles/10.3389/fendo.2026.2017813/full
AB - Diabetic wounds are characterized by persistent inflammation and impaired tissue repair, with sensory neuropathy potentially disrupting the signals that coordinate these processes. Calcitonin gene-related peptide (CGRP) has emerged as a mediator connecting sensory neurons to myeloid-cell behavior. Experimental studies show that CGRP signaling through the calcitonin receptor-like receptor and receptor activity-modifying protein 1 regulates inflammatory-cell recruitment and macrophage efferocytosis, partly through thrombospondin-1. These findings extend the proposed contribution of sensory nerves beyond protection from injury to active regulation of inflammatory resolution. However, diabetes also compromises the recognition and processing of apoptotic cells, raising the possibility that ligand supplementation alone may not restore clearance. Moreover, CGRP can impair antibacterial defense in some infection models while supporting cutaneous antifungal immunity, and thrombospondin-1 has vascular effects that differ from its clearance-promoting activities. This Mini Review critically integrates these findings with recent CGRP delivery studies, distinguishing evidence from human tissue, diabetic wound models, acute injury, and infection. We argue that therapeutic development should address both neuronal signal availability and recipient-cell competence, while evaluating microbial control and perfusion alongside repair. Local CGRP delivery is a promising preclinical strategy, but its mechanisms and therapeutic window require validation in the heterogeneous environment of human diabetic foot ulcers.
SN - 1664-2392
ER -