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微小 RNA 参与男性型脱发的病理生理学和发病机制。

MicroRNAs take part in pathophysiology and pathogenesis of Male Pattern Baldness.

机构信息

Department of Medical Genetics, Medical School, Tehran University of Medical Sciences, Poorsina Street, Tehran, Iran.

出版信息

Mol Biol Rep. 2010 Jul;37(6):2959-65. doi: 10.1007/s11033-009-9862-2. Epub 2009 Oct 10.

Abstract

Male Pattern Baldness (MPB) or androgenetic alopecia is a common form of hair loss with androgens and genetics having etiological significance. Androgens are thought to pathophysiologically power on cascades of chronically dramatic alterations in genetically susceptible scalp dermal papillas, specialized cells in hair follicles in which androgens react, and finally resulting in a patterned alopecia. However, the exact mechanisms through which androgens, positive regulators of growth and anabolism in most body sites, paradoxically exert their effects on balding hair follicles, are not yet known. The role of microRNAs, a recently discovered class of non-coding RNAs, with a wide range of regulatory functions, has been documented in hair follicle formation and their deregulation in cancer of prostate, a target organ of androgens has also been delineated. Yet, there is a lack of knowledge in agreement with microRNAs' contribution in pathophysiology of MPB. To investigate the role of microRNAs in pathogenesis of MPB, we selected seven microRNAs, predicted bioinformatically on a reverse engineering basis, from previously published microarray gene expression data and analyzed their expression in balding relative to non-balding dermal papillas. We found for the first time upregulation of four microRNAs (miR-221, miR-125b, miR-106b and miR-410) that could participate in pathogenesis of MPB. Regarding microRNAs' therapeutic potential and accessibility of hair follicles for gene therapy, these microRNAs can be considered as good candidates for a new revolutionized generation of treatments.

摘要

男性型脱发(MPB)或雄激素性脱发是一种常见的脱发形式,雄激素和遗传因素具有发病学意义。雄激素被认为在病理生理学上可以驱动一系列慢性剧烈的变化,这些变化发生在遗传易感性头皮真皮乳头、毛囊中的特化细胞中,最终导致模式性脱发。然而,雄激素在大多数身体部位是生长和合成代谢的正调节剂,却反常地对脱发毛囊产生作用的具体机制尚不清楚。microRNAs 是一类新发现的非编码 RNA,具有广泛的调节功能,其在毛囊形成中的作用及其在前列腺癌中的失调作用已有记载,而前列腺癌是雄激素的靶器官。然而,在 microRNAs 对 MPB 发病机制的贡献方面,知识仍然存在不足。为了研究 microRNAs 在 MPB 发病机制中的作用,我们根据以前发表的微阵列基因表达数据,通过反向工程的方法预测了七个 microRNAs,并分析了它们在脱发和非脱发真皮乳头中的表达情况。我们首次发现了四个 microRNAs(miR-221、miR-125b、miR-106b 和 miR-410)的上调,这些 microRNAs可能参与了 MPB 的发病机制。鉴于 microRNAs 的治疗潜力和毛囊对基因治疗的可及性,这些 microRNAs可以被视为新一代革命性治疗方法的良好候选物。

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