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Advanced Glycation Endproducts Delay Diabetic Wound Healing by OSR2/SPRR1B Signalling in Keratinocyte's Proliferation

Jiaoyong Dong1, Xiaozan Cao1, Yuzhi Jiang1

  • 1Department of Burn, Shanghai Institute of Burn, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Canadian Journal of Diabetes
|June 19, 2026
PubMed
Abstract

Insights

Advanced Glycation End-products (AGEs) impair diabetic wound healing. This study reveals the OSR2-SPRR1B axis as a key mechanism, showing that inhibiting Small proline-rich protein 1B (SPRR1B) accelerates healing in diabetic models.

Area of Science:

  • Dermatology
  • Molecular Biology
  • Biochemistry

Background:

  • Advanced Glycation End-products (AGEs) deposition in skin is a significant risk factor for non-healing diabetic wounds.
  • The precise molecular mechanisms by which AGEs impede diabetic wound healing remain largely undetermined.

Purpose of the Study:

  • To elucidate the signaling pathway and mechanism through which AGEs influence diabetic wound healing.
  • To identify key molecular targets for therapeutic intervention in diabetic wound repair.

Main Methods:

  • Bioinformatic analysis of the GEO dataset (GSE80178) to identify differentially expressed genes (DEGs) in diabetic foot ulcer (DFU) versus non-DFU tissues.
  • Validation of Small proline-rich protein 1B (SPRR1B) as a key target in clinical specimens.
  • In vitro studies using AGEs-stimulated HaCaT cells and in vivo studies with db/db diabetic mouse models.
  • Employing cellular assays, chromatin immunoprecipitation (ChIP), and in vivo shRNA knockdown to investigate the OSR2-SPRR1B axis.

Main Results:

  • SPRR1B and OSR2 were significantly upregulated in diabetic wound tissues and AGEs-treated keratinocytes.
  • Knockdown of SPRR1B or OSR2 promoted keratinocyte proliferation, inhibited apoptosis, and modulated epidermal differentiation markers (CK5/CK14, loricrin, CK1/CK10).
  • ChIP assays confirmed OSR2 directly induces SPRR1B expression, establishing the OSR2-SPRR1B axis. SPRR1B knockdown accelerated wound healing in diabetic mice, enhancing proliferation and improving epidermal differentiation.

Conclusions:

  • SPRR1B is identified as a critical mediator in AGEs-induced diabetic wound impairment.
  • OSR2 functions as an upstream regulator of SPRR1B, forming a crucial axis in diabetic wound pathology.
  • Inhibition of SPRR1B demonstrates therapeutic potential for enhancing diabetic wound healing.
Keywords:
AGEAGEsOSR2SPRR1Bdiabetic woundkeratinocyteskératinocytesplaie diabétique

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