Hair Follicle Microenvironment Changes in Collagen VI-Myopathy Patients with Alopecia

Collagen VI-related myopathies (COL6-RM) are rare hereditary disorders characterized by skeletal muscle dysfunction and skin manifestations, including keratosis pilaris, hypertrophic scars, and keloids. We recently found that alopecia is a novel and previously unrecognized scalp phenotype in COL6-RM; however, the precise pathogenetic mechanisms underlying hair follicle dysfunction in these patients remain incompletely understood. We performed a comprehensive immunohistochemical, ultrastructural, and proteomic characterization of scalp biopsies from six COL6-RM patients presenting with hair loss and scalp itching. We found structural alterations in the hair follicle extracellular matrix architecture, particularly in the inner fibrous sheath surrounding the hair follicle. In addition, the analysis of the perifollicular adipose tissue and derived cell cultures showed changes in lipid droplet size consistent with a tendency toward cell hypertrophy. Strikingly, proteomic profiling of adipokines revealed a pro-inflammatory and extracellular matrix-remodeling signature. Consistent with inflammation and extracellular matrix remodeling, CD68 macrophages and MMP2 expression were increased in the dermis of COL6-RM patients, particularly around the perifollicular adipocytes. Overall, these data indicate a complex pathological signature involving ECM and adipose tissue remodeling. In this context, collagen VI emerges as a potential regulator of the hair follicle microenvironment.