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Updated: Mar 2, 2026

Methods to Study Mrp4-containing Macromolecular Complexes in the Regulation of Fibroblast Migration
Published on: May 19, 2016
Annexin A2 functions downstream of c‑Jun N‑terminal kinase to promote skin fibroblast cell migration
Youpei Wang1, Xinmei Wu2, Qing Wang3
1Clinical Examination Center, The Affiliated Eye Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China.
Abstract:
Delayed healing of skin wounds is one of the outcomes of diabetes mellitus (DM), a condition that affects a significant number of patients worldwide. However, the underlying mechanisms remain unknown. In order to examine proteome alterations in DM, a rat model of type 1 diabetes was developed using streptozotocin injections. The proteomic responses of normal and DM rat skin were analyzed by two‑dimensional electrophoresis, and differentially expressed proteins were identified using a liquid chromatography/mass spectrometry system. DM induced 36 and repressed 41 differentially expressed proteins, respectively. Altered proteins were involved in a number of biological processes, including RNA and protein metabolism, the tricarboxylic acid cycle, glycolysis, cytoskeleton regulation, hydrogen detoxification and calcium‑mediated signal transduction. In addition, overexpression of annexin A2, one of the signaling proteins altered by DM, accelerated the rate of human skin fibroblast cell migration. Application of SP600125, an inhibitor of a key regulator of cell migration c‑Jun N‑terminal kinase (JNK), inhibited the migration of normal cells. By contrast, SP600125 treatment did not inhibit the migration of annexin A2‑overexpressed cells, indicating that annexin A2 may function downstream of JNK. In conclusion, the results of the present study reveal the potential proteomic responses to DM in skin tissues, and demonstrate a positive functional role of annexin A2 in fibroblast cell migration.
Insights
Diabetes mellitus (DM) impairs skin wound healing by altering skin proteins. This study identified specific protein changes and found annexin A2 promotes fibroblast migration, potentially aiding wound repair in diabetic patients.
Area of Science:
- Biochemistry
- Molecular Biology
- Dermatology
Background:
- Delayed skin wound healing is a common complication of diabetes mellitus (DM).
- The molecular mechanisms underlying impaired wound healing in DM are not fully understood.
- Proteomic analysis offers a way to investigate systemic changes in disease states.
Purpose of the Study:
- To identify proteomic alterations in the skin of a rat model with type 1 diabetes.
- To explore the functional role of identified differentially expressed proteins in skin wound healing.
- To investigate the potential involvement of annexin A2 in fibroblast migration.
Main Methods:
- A type 1 diabetes mellitus rat model was induced using streptozotocin injections.
- Proteomic analysis of normal and diabetic rat skin was performed using two-dimensional electrophoresis.
- Protein identification was achieved through liquid chromatography/mass spectrometry.
- Fibroblast cell migration assays were conducted with and without annexin A2 overexpression and JNK inhibition.
Main Results:
- Diabetes mellitus induced 36 and repressed 41 differentially expressed proteins in rat skin.
- Altered proteins were involved in critical cellular processes like metabolism, cytoskeleton regulation, and signal transduction.
- Overexpression of annexin A2 enhanced human skin fibroblast cell migration.
- Annexin A2 appears to function downstream of c-Jun N-terminal kinase (JNK) in regulating cell migration.
Conclusions:
- This study elucidates potential proteomic changes in skin tissues affected by diabetes mellitus.
- Annexin A2 plays a positive functional role in fibroblast cell migration, suggesting a therapeutic target for diabetic wound healing.
- Understanding these molecular mechanisms can lead to improved treatments for diabetic skin complications.
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