Topical inhibition of PUMA signaling mitigates radiation injury

Wound Repair and Regeneration : Official Publication of the Wound Healing Society [and] the European Tissue Repair Society
Maria J KowzunDaniel Ceradini

Abstract

Radiation therapy is an effective treatment strategy for many types of cancer but is limited by its side effects on normal tissues, particularly the skin, where persistent and progressive fibrotic changes occur and can impair wound healing. In this study, we attempted to mitigate the effects of irradiation on skin using a novel transcutaneous topical delivery system to locally inhibit p53 up-regulated modulator of apoptosis (PUMA) gene expression with small interfering RNA (siRNA). In an isolated skin irradiation model, the dorsal skin of C57 wild-type mice was irradiated. Prior to irradiation, PUMA and nonsense siRNA were applied via a novel hydrogel formulation to dorsal skin and reapplied weekly. Skin was harvested at multiple time points to evaluate dermal siRNA penetration, mRNA expression, protein expression, dermal thickness, subcutaneous fat, stiffness, vascular hypertrophy, SCAR index, and reactive oxygen species (ROS) generation. Murine skin treated with topical PUMA siRNA via optimized hydrogel formulation demonstrated effective PUMA inhibition in irradiated tissue at 3-4 days. Tissue stiffness, dermal thickness, vascular hypertrophy, SCAR index, ROS levels, and mRNA levels of MnSOD and TGF-β were all significantly r...Continue Reading

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Aug 20, 2019·Journal of Liposome Research·Pirthi Pal SinghRavinder Kodipyaka
Sep 4, 2021·Materials Science & Engineering. C, Materials for Biological Applications·Hye Ran LeeChul-Ho Kim

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