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Human collagen III mRNA therapy for effective skin rejuvenation

Jiamin Zhang,Shuqin Chen,Jiaqi Yang,Lianhao Song,Linfeng Chen,Wei Feng,Rong Ju,Zhi Xie

Published 2025 in Journal of Translational Medicine

ABSTRACT

Skin photoaging leads to the deterioration of dermal collagen and overall skin integrity, resulting in visible signs of aging, particularly around the eye. Collagen III plays a pivotal role in maintaining skin elasticity and facilitating proper collagen fibril organization. Messenger RNA (mRNA)-based therapeutics present a novel alternative for addressing these limitations by enabling the localized production of full-length, biologically active proteins. This study evaluates the therapeutic effects of human collagen III (hCOL3A1) mRNA on UVB-induced skin photoaging using in vitro and in vivo models. In vitro, human fibroblasts were used to assess oxidative stress, senescence, apoptosis, proliferation, and migration. In vivo, a UVB-induced murine photoaging model was used to assess skin barrier function, dermal thickness, collagen content, and senescence markers were analyzed post-treatment. Transcriptome analysis was conducted to explore gene expression changes and key pathways involved in photoaging and repair mechanisms. Our findings demonstrate that hCOL3A1 mRNA reduces oxidative stress, senescence, apoptosis and promotes cell proliferation and migration in a photoaging cell model. In a murine photoaging model, hCOL3A1 mRNA significantly improves skin barrier function, enhances dermal thickness, restores collagen content, improves dermal structure, and reduces cellular senescence markers without inducing systemic toxicity or immunogenicity. Transcriptome analyses reveal that hCOL3A1 mRNA reverses UVB-induced gene expression changes, reinstating critical signaling pathways for skin homeostasis and fibroblast function. These results highlight hCOL3A1 mRNA as a promising therapeutic candidate for skin photoaging and underscore the potential of mRNA-based therapies in dermatology and regenerative medicine.

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