In primary cicatricial alopecia, irretrievable damage of the hair follicle (HF) which is most common variant and frontal fibrosing alopecia (FFA), do results from apoptosis and pathological epithelial-mesenchymal transition (EMT) of epithelial HF stem cells (eHFSCs). This is in conjunction with the collapse of bulge immune privilege (IP) and interferon-gamma-mediated chronic inflammation. The scaffolding protein caveolin-1 (Cav1) is the important component of specialized cell membrane microdomains (caveolae) regulating multiple signaling events. Even though Cav1 is the most prominently expressed in the bulge area of human scalp HFs. It has not been investigated also in any cicatricial alopecia context. Remarkably, in mice, Cav1 is also involved in the regulation of (1) key HF IP guardians (TGF-β and α-MSH signaling), (2) IP collapse inducers or markers (IFNγ, substance P and MICA), and (3) EMT. Thus, it washypothesized that Cav1 might be an unrecognized, important performer in the pathobiology of cicatricial alopecias, and predominantly, in FFA, that is presently considered as the most common type of primary lymphocytic scarring alopecia in the whole world. It was envisioned that localized therapeutic inhibition of Cav1 of FFA management (by using cholesterol depleting agents, i.e., cyclodextrins or statins), canprevent and possibly reverse the bulge IP collapse and pathological EMT. Furthermore, manipulation of HF Cav1 expression or localization will not only be appropriate for cicatricial alopecia management, but FFA could also serve as a model disease for explaining the role of Cav1 in other stem cell- and/or IP collapse-associated pathologies.

Source: Jozic I, Chéret J, Abujamra BA, et al. Biomedicines. 2021 May 19;9(5):572. doi: 10.3390/biomedicines9050572. PMID: 34069454; PMCID: PMC8159142.