Microfibril-Associated Protein 5 Contributes to the Elastic Fiber Abnormalities in Aged Skin.

IF 1.7 4区 医学 Q3 PHARMACOLOGY & PHARMACY
Fumiaki Sato, Teruaki Oku, Yuka Nishigaki, Mana Suzuki, Hiroyasu Sakai, Hideyuki Takeshima, Yoshinori Kato
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Abstract

Elastic fibers, which contribute to the flexibility of tissues such as the skin, alveoli, and arteries, have a long half-life and are not regenerated once formed during the fetal stage. Consequently, the degradation of elastic fibers due to aging or inflammation can significantly impact tissue function. In the dermis, degeneration of elastic fibers is characterized by degradation in photoaging, driven by UV radiation, and structural abnormalities of elastic fibers in intrinsic aging. However, the mechanisms driving the abnormalities associated with intrinsic aging remain incomplete. This study aimed to identify the factors involved in the elastic fiber abnormalities associated with intrinsic aging of the dermis. Through a comprehensive analysis of gene expression, this study focused on microfibril-associated protein 5 (MFAP5) as a candidate gene responsible for the elastic fiber abnormalities associated with intrinsic aging. Immunofluorescence staining revealed that aged fibroblasts highly expressed MFAP5 and strongly localized it to aggregated elastic fibers. Furthermore, the elimination of MFAP5 expression suppressed elastic fiber aggregation. The exogenous addition of MFAP5 induced thickening and disorganization of elastic fibers, effects that were not observed with the overexpression of MFAP5 in young fibroblasts, which merely express MFAP5. Moreover, MFAP5 inhibited the interaction between latent transforming growth factor β binding protein 4 and fibulin-5, which are crucial for elastic fiber formation. These results suggest that excess MFAP5 expression associated with aging causes abnormalities in elastic fibers. Understanding the role of MFAP5 in elastic fiber abnormalities highlights its potential as a therapeutic target for mitigating intrinsic dermal aging and improving skin elasticity.

微纤维相关蛋白5与衰老皮肤弹性纤维异常有关。
弹性纤维有助于皮肤、肺泡和动脉等组织的柔韧性,其半衰期很长,在胎儿期一旦形成就不能再生。因此,由于老化或炎症,弹性纤维的降解会显著影响组织功能。在真皮中,弹性纤维的退化的特征是光老化的降解,由紫外线辐射驱动,以及弹性纤维在内在老化中的结构异常。然而,驱动与内在衰老相关的异常的机制仍然不完整。本研究旨在确定与真皮固有老化相关的弹性纤维异常的因素。通过对基因表达的综合分析,本研究将微纤维相关蛋白5 (microfibril-associated protein 5, MFAP5)作为与内在衰老相关的弹性纤维异常相关的候选基因。免疫荧光染色显示,衰老成纤维细胞高度表达MFAP5,并强烈定位于聚集的弹性纤维。此外,MFAP5表达的消除抑制了弹性纤维的聚集。外源性添加MFAP5诱导弹性纤维增厚和解体,而在仅表达MFAP5的年轻成纤维细胞中过表达MFAP5没有观察到这种作用。此外,MFAP5抑制了潜在转化生长因子β结合蛋白4和纤维蛋白5之间的相互作用,而纤维蛋白5是弹性纤维形成的关键。这些结果表明,与衰老相关的过量MFAP5表达导致弹性纤维异常。了解MFAP5在弹性纤维异常中的作用,突出了其作为缓解皮肤固有老化和改善皮肤弹性的治疗靶点的潜力。
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来源期刊
CiteScore
3.50
自引率
5.00%
发文量
247
审稿时长
2 months
期刊介绍: Biological and Pharmaceutical Bulletin (Biol. Pharm. Bull.) began publication in 1978 as the Journal of Pharmacobio-Dynamics. It covers various biological topics in the pharmaceutical and health sciences. A fourth Society journal, the Journal of Health Science, was merged with Biol. Pharm. Bull. in 2012. The main aim of the Society’s journals is to advance the pharmaceutical sciences with research reports, information exchange, and high-quality discussion. The average review time for articles submitted to the journals is around one month for first decision. The complete texts of all of the Society’s journals can be freely accessed through J-STAGE. The Society’s editorial committee hopes that the content of its journals will be useful to your research, and also invites you to submit your own work to the journals.
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