Investigating the Relevance of Cyclic Adenosine Monophosphate Response Element-Binding Protein to the Wound Healing Process: An In Vivo Study Using Photobiomodulation Treatment

Int J Mol Sci. 2024 Apr 29;25(9):4838. doi: 10.3390/ijms25094838.

Abstract

Monitoring inflammatory cytokines is crucial for assessing healing process and photobiomodulation (PBM) enhances wound healing. Meanwhile, cAMP response element-binding protein (CREB) is a regulator of cellular metabolism and proliferation. This study explored potential links between inflammatory cytokines and the activity of CREB in PBM-treated wounds. A total of 48 seven-week-old male SD rats were divided into four groups (wound location, skin or oral; treatment method, natural healing or PBM treatment). Wounds with a 6 mm diameter round shape were treated five times with an 808 nm laser every other day (total 60 J). The wound area was measured with a caliper and calculated using the elliptical formula. Histological analysis assessed the epidermal regeneration and collagen expression of skin and oral tissue with H&E and Masson's trichrome staining. Pro-inflammatory (TNF-α) and anti-inflammatory (TGF-β) cytokines were quantified by RT-PCR. The ratio of phosphorylated CREB (p-CREB) to unphosphorylated CREB was identified through Western blot. PBM treatment significantly reduced the size of the wounds on day 3 and day 7, particularly in the skin wound group (p < 0.05 on day 3, p < 0.001 on day 7). The density of collagen expression was significantly higher in the PBM treatment group (in skin wound, p < 0.05 on day 3, p < 0.001 on day 7, and p < 0.05 on day 14; in oral wound, p < 0.01 on day 7). The TGF-β/TNF-α ratio and the p-CREB/CREB ratio showed a parallel trend during wound healing. Our findings suggested that the CREB has potential as a meaningful marker to track the wound healing process.

Keywords: cAMP response element-binding protein; inflammation; photobiomodulation; wound healing.

MeSH terms

  • Animals
  • Collagen / metabolism
  • Cyclic AMP Response Element-Binding Protein* / metabolism
  • Cytokines / metabolism
  • Low-Level Light Therapy* / methods
  • Male
  • Phosphorylation / radiation effects
  • Rats
  • Rats, Sprague-Dawley*
  • Skin / injuries
  • Skin / metabolism
  • Skin / pathology
  • Skin / radiation effects
  • Transforming Growth Factor beta / metabolism
  • Tumor Necrosis Factor-alpha / metabolism
  • Wound Healing* / radiation effects

Substances

  • Cyclic AMP Response Element-Binding Protein
  • Cytokines
  • Tumor Necrosis Factor-alpha
  • Collagen
  • Transforming Growth Factor beta