Expression of matrix metalloproteinases and tissue inhibitor of matrix metalloproteinases in the hair cycle

Abstract

According to the growth state of hair follicles, the hair cycle is divided into the anagen, catagen and telogen phases. A number of biological factors have been shown to synchronize with the hair cycle. As an important component of the hair follicle, the extracellular matrix is regulated by matrix metalloproteinases (MMPs) and their inhibitors (tissue inhibitor of matrix metalloproteinases; TIMPs). It has been reported that MMP-2, MMP-9 and TIMP-1 are associated with the hair cycle; however, their expression levels during the hair cycle have not been fully elucidated. Reverse transcription-polymerase chain reaction and ELISA analysis in the present study demonstrated that, during the hair cycle in mice, mRNA and protein expression levels of MMP-2 and MMP-9 were elevated in the anagen phase, and decreased during the catagen and telogen phases. Furthermore, SDS-PAGE gelatin zymography demonstrated that their activities fluctuated in the hair cycle. Additionally, it was observed that the mRNA and protein expression levels of TIMP-1 and TIMP-2 were negatively correlated with MMP-9 and MMP-2, respectively. Immunohistochemical examination demonstrated that MMP-2 and TIMP-2 were present in all structures of the hair follicle. However, MMP-9 and TIMP-1 were locally expressed in certain areas of the hair follicle, such as in the sebaceous gland at the anagen, catagen and telogen phases, and in the inner root sheath at the catagen phase. These results suggested that MMP-2 and MMP-9 may serve an important role in the hair growth cycle. Introduction The hair cycle is an intrinsic and cyclic system of regenerating tissue (1), which is composed of the anagen (phases of rapid growth; 1-3 weeks), catagen (phases of apoptosis-driven regression; ~2 days) and telogen (phases of relative quiescence; ~2 weeks) phases (Fig. 1). The growth of hair is considered to be a result of the cyclic remodeling of the follicle (2). There are numerous biological factors that regulate or synchronize with the hair cycle (3), such as hormones, growth factors, enzymes and transcriptional factors. Enzymes include ornithine decarboxylase, aromatase and nexin 1. The hair cycle is considered to be a process of tissue regeneration associated with extracellular matrix (ECM) degradation and remodeling (4). Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases that can be produced by a number of different types of cells in the skin, including fibroblasts, keratinocytes, macrophages, endothelial cells, mast cells and eosinophils (5). MMPs consist of at least 19 cloned membranes, including the type IV collagenases (such as MMP-2 and MMP-9), metalloelastase, interstitial collagenase, stromelysins, matrilysins and membrane-type MMPs. In addition, increasing evidence demonstrates that MMPs can affect the signaling pathways associated with various factors, such as insulin-like growth factor-binding protein-3, tumor necrosis factor-α (TNF-α), fibroblast growth factor receptor 1 and angiogenic factors (6-10). MMP-2 and MMP-9 are important members of the MMP superfamily, since they can degrade gelatin, collagen IV, V, VII and X, fibronectin, and elastin (9-13). The expression levels of MMP-2 and MMP-9 are reported to be regulated by numerous factors. For instance, MMP-2 is regulated by transforming growth factor (TGF)-β, interleukin (IL)-1β and interferon (IFN) in certain fibroblasts (14‐17), and Wnt in T cells (18). Similarly, MMP-9 is induced by several regulators, including epidermal growth factor, TGF-α, TGF-β, IL-1β and IFN-α (16,19-23). The activities of MMP-2 and MMP‐9 are specifically inhibited by tissue inhibitor of matrix metalloproteinases (TIMP)-2 and TIMP-1, respectively (24), which may be vital in the regulation of connective tissue metabolism and remodeling in numerous different organ systems, including hair follicle. There are a few studies investigating the relationship between MMP-2, MMP-9, TIMP-1 and the hair cycle (25). Expression of matrix metalloproteinases and tissue inhibitor of matrix metalloproteinases in the hair cycle CHUN HOU, YONG MIAO, XUE WANG, CHAOYUE CHEN, BOJIE LIN and ZHIQI HU Department of Plastic and Cosmetic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China Received February 6, 2015; Accepted March 15, 2016 DOI: 10.3892/etm.2016.3319 Correspondence to: Dr Zhiqi Hu, Department of Plastic and Cosmetic Surgery, Nanfang Hospital, Southern Medical University, 1838 Guangzhou Avenue North, Guangzhou, Guangdong 510515,

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@inproceedings{Hou2016ExpressionOM, title={Expression of matrix metalloproteinases and tissue inhibitor of matrix metalloproteinases in the hair cycle}, author={Chun Hou and Yong Miao and Xue Wang and C Chen and Bojie Lin and Zhiqi Hu}, year={2016} }