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صفحه اصلی
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4th international edition and 13th Iranian Conference on Bioinformatics
Iron, Oxidative Stress, and Skin Aging: The Therapeutic Potential of TGF-β1 Modulation
نویسندگان :
Maryam Kaboli
1
Amir Amiri-Yekta
2
Seyed Abolhassan Shahzadeh Fazeli
3
Yasser Tahamtani
4
1- Royan
2- Royan
3- royan
4- Royan
کلمات کلیدی :
Skin Rejuvenation،Iron Deposition،TGF-β1 Signaling Pathway،Intrinsic Aging،Extrinsic Aging
چکیده :
Background: Aging is a biological process causing a gradual, irreversible decline in physical function across all organ systems. It is believed that the aging process begins at different times in different systems, and the skin is one of the first organs to age [Shinde and Deore, 2022], which is not only a cosmetic issue, as it can lead to various dermatological disorders that significantly affect the quality of life of older individuals. These disorders range from pruritus to more serious conditions like melanomas [Kühnel and Pasztorek, 2024]. Iron accumulates in various organs, including the skin, with age, and excess iron can induce oxidative stress through the generation of ROS by the Fenton reaction, which also Iron chelators treatment suppresses the UV radiation-induced upregulation of MMPs and delays skin photodamage. [Liu and Chen, 2022], investigated the effect of blood donation on skin aging by analyzing histological and clinical changes in old mice and found that blood donation reduces the signs of skin aging by increasing collagen synthesis and decreasing collagen degradation. The improvement in skin aging due to blood donation is associated with a reduction in iron deposits and an increase in TGF-β1 in the elderly skin. Objectives: This study aimed to investigate the role of TGFB1 in humans and to compare it with that in a mouse model to predict the role of blood donation and its effects on skin rejuvenation. Materials and methods: We performed a protein BLAST search using NCBI to retrieve the protein sequences of TGFB1 in both Mus musculus and Homo sapiens. Next, we identified the TGF-β signaling pathway using KEGG, focusing on key components, such as TGFBR1, TGFBR2, SMAD proteins, and collagen-related genes (COL1A1 and COL3A1). Protein-protein interaction networks were analyzed using STRING to explore the functional similarities between the species. For structural analysis, the 3D structure of TGFB1 was modeled and aligned for both species using PyMOL. Functional sites of the proteins were extracted using UniProt and compared using PyMOL. Results: Based on the comprehensive bioinformatics analyses conducted in this study, a high degree of similarity between mouse and human systems was confirmed at both the sequence and structural levels. Alignment of the key proteins involved in the TGF-β and PI3K/Akt signaling pathways revealed significant conservation in their sequences, functional domains, and three-dimensional structures. Pathway enrichment analysis indicated that the core components and interactions within these signaling cascades were highly conserved between the two species, suggesting a functional similarity. Additionally, gene expression data supported parallel patterns of expression for genes associated with collagen synthesis (COL1A1 and COL3A1) and tissue remodeling. Conclusion: Our results align with the findings of a study by [Kühnel and Pasztorek, 2024], which demonstrated that Platelet-Rich Plasma derived from human blood promotes skin rejuvenation by upregulating COL1 and COL3 expression through activation of TGF-β signaling. These findings, combined with the structural and pathway-level similarities observed in this study, support the potential translational application of mouse models in human clinical studies focused on skin rejuvenation and anti-aging therapies.
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بیشتر
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