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. 2022 Aug 3;23(15):8621.
doi: 10.3390/ijms23158621.

Wound Healing Impairment in Type 2 Diabetes Model of Leptin-Deficient Mice-A Mechanistic Systematic Review

Albert Stachura  1   2 , Ishani Khanna  1 , Piotr Krysiak  1 , Wiktor Paskal  1 , Paweł Włodarski  1
Affiliations

Wound Healing Impairment in Type 2 Diabetes Model of Leptin-Deficient Mice-A Mechanistic Systematic Review

Albert Stachura et al. Int J Mol Sci. .

Abstract

Type II diabetes mellitus (T2DM) is one of the most prevalent diseases in the world, associated with diabetic foot ulcers and impaired wound healing. There is an ongoing need for interventions effective in treating these two problems. Pre-clinical studies in this field rely on adequate animal models. However, producing such a model is near-impossible given the complex and multifactorial pathogenesis of T2DM. A leptin-deficient murine model was developed in 1959 and relies on either dysfunctional leptin (ob/ob) or a leptin receptor (db/db). Though monogenic, this model has been used in hundreds of studies, including diabetic wound healing research. In this study, we systematically summarize data from over one hundred studies, which described the mechanisms underlying wound healing impairment in this model. We briefly review the wound healing dynamics, growth factors' dysregulation, angiogenesis, inflammation, the function of leptin and insulin, the role of advanced glycation end-products, extracellular matrix abnormalities, stem cells' dysregulation, and the role of non-coding RNAs. Some studies investigated novel chronic diabetes wound models, based on a leptin-deficient murine model, which was also described. We also discussed the interventions studied in vivo, which passed into human clinical trials. It is our hope that this review will help plan future research.

Keywords: db/db; diabetes; leptin; mice; molecular mechanisms in wound healing; ob/ob; wound; wound healing; wound healing in chronic disease; wound healing in metabolic disease.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
PRISMA flowchart of article selection.
Figure 2
Figure 2
Leptin acting as a mitogen in wound healing. JAK-STAT—Janus kinase-signal transduction and transcription activation.
Figure 3
Figure 3
Effect of AGEs (advanced glycation end-products) on wound healing process. MAPK—mitogen-activated protein kinase.
Figure 4
Figure 4
CXCR4/CXCL12-dependent stem cell function in wound healing. HSCs—hemapoietic stem cells, EPCs—endothelial progenitor cells, pMAPK—phosphorylated mitogen-activated protein kinase, CXCR—CXC chemokine receptor, SDF—stromal cell-derived factor, CXCL—CXC chemokine ligand, CD—cluster of differentiation, IL-6—interleukin 6, MIP 2—macrophage inflammatory protein 2.
See this image and copyright information in PMC

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