(WHS-K3.05) SUBCUTANEOUS INJECTION OF ZEIN, A DIETARY PROTEIN, HAS POSITIVE WOUND HEALING EFFECTS THAT ARE PREVENTED BY FINGOLIMOD (FTY720) TREATMENT
Thursday, May 16, 2024
9:15 AM – 10:15 AM East Coast USA Time
Pathological scars resulting from impairment or modification in wound healing are serious problems for patients' health and strongly impact the financial cost of their treatment. Pathological scars, such as hypertrophic scars and keloids, are common even in cases of scheduled surgery. Exacerbated and prolonged inflammation is an important factor in the occurrence of wound healing problems. The search for more effective forms of intervention that prevent pathological scars requires a better understanding of the cellular interactions that occur during repair. Previous work has shown that parenteral injection of dietary proteins, concomitant with skin lesions in mice, reduces the inflammatory infiltrate in the wound bed and improves healing. Zein is a corn protein present in mouse food and one injection of zein in Al(OH)3 concomitantly with skin wounds reduces the inflammatory infiltrate, increases the number of T lymphocytes in the wound bed and improves healing (https://doi.org/10.1590/1414-431X2021e11735). To evaluate whether the positive effects of zein injection on the repair of skin lesions depend on the circulation of lymphocytes, we used FTY720 (Fingolimod), a drug that sequesters lymphocytes in lymph nodes. Male C57BL/6 mice, 8 weeks old, received intraperitoneal injections of 1mg/kg of FTY720 two days before injury, on the day of injury and two days after skin injury (CEUA/UFMG protocol 253/2021). Two lesions on the back skin were made with a 6mm dermatological punch and the animals in the experimental group also received one subcutaneous injection of 10 microgram of zein in 1.6 mg of Al(OH)3, at the base of the tail. Skin analyzes performed at 7 and 40 days after the injuries showed that, in the absence of FTY720, the injection of zein concomitantly with the injuries reduced the inflammatory infiltrate, increased the number of T lymphocytes in the wound bed and improved the organization of the extracellular matrix in the neodermis. At 7 days after the injuries, it was noted that the injection of FTY720 delayed the detachment of the wound crust and increased the number of leukocytes (CD45+), neutrophils (Ly6G+) and macrophages (F4/80+) in the wound bed. Furthermore, FTY720 treatment altered the morphological characteristics of fibroblasts seen after H&E staining, suggesting greater activation of these cells. At 40 days after the injuries, the neodermis of animals that received injection of zein showed an organization of the extracellular matrix similar to that of intact skin but, on the contrary, those that received FTY720 and zein showed a larger scar, with thinner fibers organized parallel to the epidermis, with characteristics of a loose matrix and larger scar. In conclusion, FTY720 prevented the increase of T lymphocytes in the wound bed and the positive effects of zein on wound healing, showing that the positive effects of zein depend on circulating lymphocytes.