Photo Credit: iStock.com/JOSE LUIS CALVO MARTIN & JOSE ENRIQUE GARCIA-MAURIÑO MUZQUIZ

Keratinocyte Arginase1 promotes wound closure by modulating inflammatory signals and lipocalin-2, revealing a therapeutic avenue for chronic skin ulcers. 

A research study published in the June 2025 issue of British Journal of Dermatology regarding Chronic skin wounds impairment and re-epithelialization due to abnormal keratinocyte migration and heightened inflammatory signaling, while the role of keratinocyte-expressed arginase 1 (ARG1) in wound closure remained unclear.  

Researchers analyzed the role of ARG1 in keratinocyte-mediated wound closure and inflammatory responses.  

They performed in vitro 2D wound assays using keratinocytes with ARG1 inhibition to investigate its role in scratch wound closure and ARG1 expression was also analyzed in human skin wound samples to assess its relevance in the wound healing process.  

The results showed that ARG1 was highly expressed in perilesional areas of acute wounds but was dysregulated in chronic ulcers, with elevated levels in the upper hyperplastic epidermis. Inhibiting ARG1 in keratinocytes reduced 2D scratch closure, increased interleukin 1 (IL-1) family and tumor necrosis factor alpha (TNFα)-driven inflammatory signaling, and significantly lowered lipocalin 2 (LCN2) expression. LCN2 expression was partially reliant on Janus Kinase/Signal Transducer and Activator of Transcription (JAK/STAT) signaling. Neutralizing LCN2 delayed scratch wound repair, and ARG1 inhibition reduced LCN2 induction after bacterial stimulation. Treatment with ARG1-derived metabolites, putrescine (Put) and urea restored both keratinocyte migration and LCN2 levels in ARG1-inhibited cells.  

Investigators concluded that ARG1 played a key role in keratinocyte re-epithelialization by modulating inflammation and antimicrobial responses, with its downstream products partially restoring wound healing in ARG1-inhibited conditions. 

Source: academic.oup.com/bjd/advance-article/doi/10.1093/bjd/ljaf223/8159930