Suppressed Paracrine Signaling of Cystatin a from Keratinocytes to Fibroblasts and Endotheliocytes Delays Wound Healing in Diabetes
- 1Department of Vascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
Abstract
Impaired wound healing in diabetes involves disrupted communication between epidermal keratinocytes and dermal cells, yet the underlying regulatory factors remain incompletely understood. This study investigated the potential role of cystatin A (CSTA) in diabetic wound repair. CSTA expression was examined in high-glucose-treated keratinocytes and diabetic mouse skin. RNA sequencing and functional assays were performed to evaluate the effects of recombinant CSTA on human dermal fibroblasts and microvascular endothelial cells, while topical CSTA and calcipotriol were evaluated in diabetic C57BL/6J mouse wound models. CSTA expression was reduced under high-glucose and diabetic conditions. Recombinant CSTA enhanced fibroblast migration and proliferation-associated activity, promoted extracellular matrix-related gene expression, and improved endothelial migration and tube formation. Topical CSTA treatment accelerated wound closure, increased CD31-positive vascular structures, and enhanced collagen deposition in diabetic mice. Calcipotriol treatment similarly improved wound repair outcomes. These findings suggest that CSTA may contribute to the regulation of dermal repair processes and highlight its potential therapeutic relevance in diabetic wound healing, although the causal contribution of endogenous CSTA deficiency remains to be established.
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BibTeX
@article{zhu2026suppressed,
title = {{Suppressed Paracrine Signaling of Cystatin a from Keratinocytes to Fibroblasts and Endotheliocytes Delays Wound Healing in Diabetes}},
author = {Bingjie Zhu and Yuchen Zhu and Ruikang Gao and Yiming Huang and Peng Zhou and Qin Li},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27219800},
url = {https://www.mdpi.com/1422-0067/27/21/9800},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Suppressed Paracrine Signaling of Cystatin a from Keratinocytes to Fibroblasts and Endotheliocytes Delays Wound Healing in Diabetes
AU - Bingjie Zhu
AU - Yuchen Zhu
AU - Ruikang Gao
AU - Yiming Huang
AU - Peng Zhou
AU - Qin Li
PY - 2026
DA - 2026/10/31
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27219800
UR - https://www.mdpi.com/1422-0067/27/21/9800
AB - Impaired wound healing in diabetes involves disrupted communication between epidermal keratinocytes and dermal cells, yet the underlying regulatory factors remain incompletely understood. This study investigated the potential role of cystatin A (CSTA) in diabetic wound repair. CSTA expression was examined in high-glucose-treated keratinocytes and diabetic mouse skin. RNA sequencing and functional assays were performed to evaluate the effects of recombinant CSTA on human dermal fibroblasts and microvascular endothelial cells, while topical CSTA and calcipotriol were evaluated in diabetic C57BL/6J mouse wound models. CSTA expression was reduced under high-glucose and diabetic conditions. Recombinant CSTA enhanced fibroblast migration and proliferation-associated activity, promoted extracellular matrix-related gene expression, and improved endothelial migration and tube formation. Topical CSTA treatment accelerated wound closure, increased CD31-positive vascular structures, and enhanced collagen deposition in diabetic mice. Calcipotriol treatment similarly improved wound repair outcomes. These findings suggest that CSTA may contribute to the regulation of dermal repair processes and highlight its potential therapeutic relevance in diabetic wound healing, although the causal contribution of endogenous CSTA deficiency remains to be established.
SN - 1422-0067
ER -