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

• Published in: International journal of molecular sciences Vol. 25; no. 9; p. 4838
• Main Authors: Kim, Sungyeon, Park, Jion, Choi, Younghoon, Jeon, Hongbae, Lim, Namkyu
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.05.2024
• Subjects: Adenosine; Adenylic acid; Analysis; Animals; cAMP response element-binding protein; Care and treatment; Collagen; Collagen - metabolism; Cyclic adenylic acid; Cyclic AMP Response Element-Binding Protein - metabolism; Cytokines; Cytokines - metabolism; Inflammation; Lasers; Low-Level Light Therapy - methods; Male; Phosphorylation - radiation effects; photobiomodulation; Protein binding; Proteins; Rats; Rats, Sprague-Dawley; Skin; Skin - injuries; Skin - metabolism; Skin - pathology; Skin - radiation effects; Transforming Growth Factor beta - metabolism; Transforming growth factors; Tumor Necrosis Factor-alpha - metabolism; Wound healing; Wound Healing - radiation effects; Wounds and injuries; South Korea; photobiomodulation; wound healing; cAMP response element-binding protein; inflammation
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms25094838

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 ( < 0.05 on day 3, < 0.001 on day 7). The density of collagen expression was significantly higher in the PBM treatment group (in skin wound, < 0.05 on day 3, < 0.001 on day 7, and < 0.05 on day 14; in oral wound, < 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.