Centre for Skin Sciences, School of Life Sciences, University of Bradford, Bradford, UK.
Cell Cycle. 2012 Feb 1;11(3):468-74. doi: 10.4161/cc.11.3.19058.
Skin development, postnatal growth and regeneration are governed by complex and well-balanced programs of gene activation and silencing. The crosstalk between small non-coding microRNAs (miRNAs) and mRNAs is highly important for steadiness of signal transduction and transcriptional activities as well as for maintenance of homeostasis in many organs, including the skin. Recent data demonstrated that the expression of many genes, including cell type-specific master transcription regulators implicated in the control of skin development and homeostasis, is regulated by miRNAs. In addition, individual miRNAs could mediate the effects of these signaling pathways through being their downstream components. In turn, the expression of a major constituent of the miRNA processing machinery, Dicer, can be controlled by cell type-specific transcription factors, which form negative feedback loop mechanisms essential for the proper execution of cell differentiation- associated gene expression programs and cell-cell communications during normal skin development and regeneration. This review summarizes the available data on how miRNA/mRNA regulatory networks are involved in the control of skin development, epidermal homeostasis, hair cycle-associated tissue remodeling and pigmentation. Understanding of the fundamental mechanisms that govern skin development and regeneration will contribute to the development of new therapeutic approaches for many pathological skin conditions by using miRNA-based interventions.
皮肤的发育、出生后的生长和再生受复杂且平衡的基因激活和沉默程序调控。小非编码 microRNAs(miRNAs)和 mRNAs 之间的串扰对于信号转导和转录活性的稳定性以及许多器官(包括皮肤)的内稳态的维持非常重要。最近的数据表明,许多基因的表达受到 miRNAs 的调控,包括参与皮肤发育和内稳态控制的细胞类型特异性主转录调控因子。此外,个别 miRNAs 可以通过作为这些信号通路的下游成分来介导其作用。反过来,miRNA 加工机制的主要成分 Dicer 的表达可以被细胞类型特异性转录因子控制,这些转录因子形成负反馈回路机制,对于正常皮肤发育和再生过程中细胞分化相关基因表达程序和细胞间通讯的正确执行至关重要。这篇综述总结了关于 miRNA/mRNA 调控网络如何参与皮肤发育、表皮内稳态、毛发周期相关组织重塑和色素沉着控制的现有数据。对调控皮肤发育和再生的基本机制的理解将有助于通过 miRNA 为基础的干预措施为许多病理性皮肤状况开发新的治疗方法。