Work

11β-HSD1-Mediated Cortisol Signalling in Fibrosis and Impaired Diabetic Wound Healing: Current Evidence and Emerging Mechanisms

Year: 2026

Type: article

Abstract: Diabetic wound healing is characterised by persistent inflammation, impaired angiogenesis, extracellular matrix (ECM) dysregulation, and defective tissue remodelling, frequently resulting in chronic wounds such as diabetic foot ulcers (DFUs). Fibrosis, characterised by excessive ECM deposition and sustained fibroblast activation, is increasingly recognised as an important barrier to effective wound repair in patients with diabetes. Emerging evidence suggests that glucocorticoid signalling, particularly through the stress hormone cortisol and its activating enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), may contribute to pathological and fibrotic changes in diabetic skin by altering inflammation, extracellular matrix turnover, angiogenesis, and cellular behaviour. In parallel, connective tissue growth factor (CTGF) and insulin-like growth factor binding protein-5 (IGFBP-5) have been associated with profibrotic processes, although the evidence for their roles in diabetic wound healing is limited, particularly for IGFBP-5. This review examines current evidence regarding the role of 11β-HSD1-mediated cortisol signalling in fibrosis and impaired diabetic wound healing, with particular emphasis on its potential interactions with CTGF and IGFBP-5. However, whether and how these mediators interact with cortisol signalling in diabetic wounds remains poorly understood. Evidence from preclinical and early clinical studies suggests that inhibition of 11β-HSD1 may improve wound repair and tissue integrity; however, many existing studies rely on acute wound models and do not fully reflect the chronic inflammatory and fibrotic environment of diabetic wounds.

Source: Diabetology

DOI: 10.3390/diabetology7100193

Authors: Lao C., Alcacer-Pitarch B., Patterson S., Tiganescu A., Wright C.S

Language: English

Topic: Wound Healing and Treatments

Subfield: Surgery

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $1,448

Funder: British Skin Foundation