Identification of Biomarkers for Footpad Dermatitis Development and Wound Healing

Footpad dermatitis (FPD) is a type of skin inflammation that causes necrotic lesions on the plantar surface of the footpads in commercial poultry, with significant animal welfare, and economic implications. To identify biomarkers for FPD development and wound healing, a battery cage trial was conducted in which a paper sheet was put on the bottom of cages to hold feces to induce FPD of broilers. Day-of-hatch Ross 308 male broiler chicks were fed a corn-soybean meal diet and assigned to 3 treatments with 8 cages per treatment and 11 birds per cage. Cages without paper sheets were used as a negative control (NEG). Cages with paper sheets during the entire growth period (d 0-30) were used as a positive control (POS) to continually induce FPD. Cages with paper sheets during d 0-13 and without paper sheets during d 14-30 were used to examine the dynamic of FPD development and lesion wound healing (LWH). Footpad lesions were scored to grade (G) 1-5 with no lesion in G1 and most severe lesion in G5. Covering with paper sheets in POS and LWH induced 99% incidence of G3 footpads on d 13. Removing paper sheets from LWH healed footpad lesions by d 30. One representative bird, with lesions most close to pen average lesion score, was chosen to collect footpad skin samples for biomarker analysis. Total collagen protein and mRNA levels of tenascin X (TNX), type I α1 collagen (COL1A1), type III α1 collagen (COL3A1), tissue inhibitor of metalloproteinase 3 (TIMP3), and integrin α1 (ITGA1) mRNA levels were decreased (P < 0.05), while mRNA levels of tenascin C (TNC), tumor necrosis factor (TNF) α, Toll-like receptor (TLR) 4 and vascular endothelial growth factor (VEGF), IL-1β, and the ratio of MMP2 to all TIMP were increased (P < 0.03) in G3 footpads in POS and LWH compared to G1 footpads in NEG on d 14. These parameters continued to worsen with development of more severe lesions in POS. After paper sheets were removed (i.e., LWH), levels of these parameters gradually or rapidly returned to levels measured in NEG. Regression analysis indicated significant quadratic changes of these parameters to footpad lesion scores. In summary, these biomarkers were interrelated with dynamic changes of footpad lesion scores, suggesting they may be used as potential biomarkers for footpad lesion development and wound healing process.