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CXCL5 suppression recovers neovascularization and accelerates wound healing in diabetes mellitus

Ching Chen1,2, Liang-Yu Lin2,3, Jaw-Wen Chen1,2,4,5,6,7

  • 1Department and Institute of Pharmacology, National Yang Ming Chiao Tung University, Taipei, Taiwan.

Cardiovascular Diabetology
|July 7, 2023
PubMed
Abstract

Insights

Higher chemokine C-X-C motif ligand 5 (CXCL5) levels are linked to type 2 diabetes. Suppressing CXCL5 improves blood vessel formation and wound healing in diabetic models by targeting CXCR2.

Area of Science:

  • Endocrinology and Metabolism
  • Vascular Biology
  • Immunology

Background:

  • Elevated chemokine C-X-C motif ligand 5 (CXCL5) levels are observed in type 2 diabetes mellitus (DM) patients.
  • The specific role of CXCL5 in diabetic vasculopathy, particularly in neovascularization and wound healing, remains unclear.

Purpose of the Study:

  • To investigate the impact of CXCL5 on neovascularization and wound healing in diabetes mellitus.
  • To elucidate the underlying mechanisms by which CXCL5 influences these processes in diabetic conditions.

Main Methods:

  • In vitro studies utilized endothelial progenitor cells (EPCs) and human aortic endothelial cells (HAECs).
  • In vivo studies employed streptozotocin-induced diabetic mice, Leprdb/JNarl mice, and CXCL5 knockout diabetic mice.
  • Functional assessments included hindlimb ischemia, aortic ring assays, matrigel plug assays, and wound healing assays.

Main Results:

  • CXCL5 levels were increased in plasma and EPCs from type 2 DM patients.
  • CXCL5 neutralization upregulated VEGF/SDF-1, enhancing cell function and promoting neovascularization and wound healing in diabetic models.
  • CXCL5 promoted inflammation (IL-1β, IL-6, TNF-α) and suppressed VEGF/SDF-1 via ERK/p65 activation through CXCR2.

Conclusions:

  • Suppression of CXCL5 enhances neovascularization and wound healing in diabetes by acting through the CXCR2 pathway.
  • CXCL5 represents a potential therapeutic target for managing vascular complications associated with diabetes mellitus.
Keywords:
CXCL5CXCR2Diabetes mellitusNeovascularizationWound healing

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