Molecular Aspects of the Pathogenesis of Androgenetic Alopecia

Abstract

The main regulators of the anagen phase of the hair follicle are dermal papillae and their sources - dermal fibroblasts of the extracellular matrix. Epithelial-mesenchymal interactions of the extracellular matrix are carried out by a number of proteinases, of which matrix metaloproteinases play an important role. Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases that can be produced by various types of skin cells, including fibroblasts, keratinocytes, macrophages, endothelial cells, mast cells, and eosinophils. Matrix metalloproteinases are composed of at least 19 cloned membranes, including type IV collagenases (such as MMP-2 and MMP-9), metalloelastase, interstitial collagenase, stromelysins, matrilisins, and membrane-type MMPs. In addition, growing evidence demonstrates that Matrix metalloproteinases can influence 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. We examined 85 males with androgenic alopecia aged 18 to 41 years. The distribution of patients with androgenic alopecia, depending on the duration of the pathological process, showed that the main number of those who seek advice from a dermatologist are patients with a disease duration from 1 to 5 years - 51.6%, as well as up to 1 year - 24.8% and from 5 to 10 years - 23.6%. The study of the concentration of inhibitors of matrix metalloproteinases (TIMP1) in patients with androgenic alopecia showed a significant decrease in its level compared to the same indicators in the control group. Thus, with the M3 type, the TIMP1 concentration was 2.01 ± 0.18 pg / ml (P <0.001), with the C2-C3 type - 1.49 ± 0.022 pg / ml (P <0.001), with the U1 type - 0.88 ± 0.054pg / ml (P <0.001). In the control group, the same indicator was 3.7 ± 0.09pg / ml. In our study, reliably low TIMP1 values in androgenic alopecia are associated, on the one hand, with the observed oxidative stress in the extracellular matrix and the inflammatory process, in which the release of reactive oxygen species occurs in parallel with a decrease in the TIMP1 level and, accordingly, an increase in the level of matrix metalloproteinases. The studies have proved the important role of the parameters of the activity of the extracellular matrix and apoptotic factors in androgenic alopecia, which lead to the inflammatory process and subsequent atrophy of the hair follicles.