He L, Zhu C, Yu XY, Dou HC, Shu MG. C1q tumor necrosis factor associated protein 3 protects HaCaT via phosphoinositide 3-kinase/protein kinase B activation by PTEN reduction. World J Diabetes 2026; 17(4): 114061 [DOI: 10.4239/wjd.v17.i4.114061]
Corresponding Author of This Article
Mao-Guo Shu, MD, Doctor, Department of Plastic, Aesthetic and Maxillofacial Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, No. 277 Yanta West Road, Xi’an 710061, Shaanxi Province, China. maoguoshu@xjtu.edu.cn
Research Domain of This Article
Endocrinology & Metabolism
Article-Type of This Article
Basic Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Diabetes. Apr 15, 2026; 17(4): 114061 Published online Apr 15, 2026. doi: 10.4239/wjd.v17.i4.114061
C1q tumor necrosis factor associated protein 3 protects HaCaT via phosphoinositide 3-kinase/protein kinase B activation by PTEN reduction
Lin He, Chan Zhu, Xue-Yuan Yu, Hui-Cong Dou, Mao-Guo Shu
Lin He, Xue-Yuan Yu, Hui-Cong Dou, Mao-Guo Shu, Department of Plastic, Aesthetic and Maxillofacial Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China
Chan Zhu, Department of Burns and Cutaneous Surgery, Xijing Hospital, Air Force Medical University, Xi’an 710032, Shaanxi Province, China
Co-first authors: Lin He and Chan Zhu.
Author contributions: Shu MG designed and coordinated the study; He L and Zhu C performed the experiments, acquired and analyzed data, wrote the manuscript; Yu XY and Dou HC interpreted the data; all authors approved the final version of the article.
Supported by the Key Research and Development Plan of Shaanxi Province of China, No. 2023-YBSF-179; and Scientific Research Fund of The First Affiliated Hospital of Xi’an Jiaotong University, No. 2021ZYTS-35.
Institutional animal care and use committee statement: The study was approved by the Ethics Committee of Xi’an Jiaotong University School of Medicine (approval No. 2023-65).
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Data sharing statement: No additional data are available.
Corresponding author: Mao-Guo Shu, MD, Doctor, Department of Plastic, Aesthetic and Maxillofacial Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, No. 277 Yanta West Road, Xi’an 710061, Shaanxi Province, China. maoguoshu@xjtu.edu.cn
Received: September 15, 2025 Revised: November 12, 2025 Accepted: February 6, 2026 Published online: April 15, 2026 Processing time: 216 Days and 2.2 Hours
Abstract
BACKGROUND
Delayed wound repair is commonly observed among individuals with diabetes.
AIM
To determine the mechanism of C1q tumor necrosis factor associated protein 3 (CTRP3) in regulation of wound healing.
METHODS
Wounds were created in wild-type C57BL/6J and db/db diabetic mice. CTRP3 expression was measured in mouse blood on days 0, 4, 8, 12, 16 and in high glucose-treated HaCaT cells. CTRP3’s role was assessed via cell growth and migration assays. Vascular endothelial growth factor (VEGF) levels were detected. A phospho-kinase array identified phosphorylated kinases. Co-immunoprecipitation verified CTRP3 interaction with phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) pathway proteins.
RESULTS
CTRP3 expression increased significantly with the passage of wound healing time and CTRP3 expression is low in high-glucose-treated HaCaT cells. High glucose treatment significantly suppressed the cell growth and migration of HaCaT cells, while high expression of CTRP3 reversed the effects of high glucose. Meanwhile, the growth factor VEGF down-regulated by high glucose treatment in HaCaT cells significantly elevated in HaCaT cells with highly-expressed CTRP3. CTRP3 promotes wound healing in diabetic mice in vivo. Moreover, CTRP3 activates PI3K/AKT pathway by reducing PTEN protein level.
CONCLUSION
CTRP3 accelerates diabetic wound healing, potentially by protecting keratinocytes through downregulating PTEN and activating the PI3K/AKT pathway, presenting a novel therapeutic target.
Core Tip: High expression of C1q tumor necrosis factor associated protein 3 (CTRP3) promotes the wound healing of diabetic mice, and this may related to the protective effects on keratinocytes. The underlying mechanism is linked to the activation of phosphoinositide 3-kinase/protein kinase B pathway by reducing the PTEN protein level. Taken together, CTRP3 may be a novel target to accelerate the wound healing in diabetes.
