A cell membrane-level approach to cicatricial alopecia management: Is caveolin-1 a viable therapeutic target in frontal fibrosing alopecia?

Ivan Jozic, Jérémy Chéret, Beatriz Abdo Abujamra, Mariya Miteva, Jennifer Gherardini, Ralf Paus

Research output: Contribution to journalArticlepeer-review

Abstract

Irreversible destruction of the hair follicle (HF) in primary cicatricial alopecia and its most common variant, frontal fibrosing alopecia (FFA), results from apoptosis and pathological epithelial-mesenchymal transition (EMT) of epithelial HF stem cells (eHFSCs), in conjunction with the collapse of bulge immune privilege (IP) and interferon-gamma-mediated chronic inflamma-tion. The scaffolding protein caveolin-1 (Cav1) is a key component of specialized cell membrane microdomains (caveolae) that regulates multiple signaling events, and even though Cav1 is most prominently expressed in the bulge area of human scalp HFs, it has not been investigated in any cicatricial alopecia context. Interestingly, in mice, Cav1 is involved in the regulation of (1) key HF IP guardians (TGF-β and α-MSH signaling), (2) IP collapse inducers/markers (IFNγ, substance P and MICA), and (3) EMT. Therefore, we hypothesize that Cav1 may be an unrecognized, important player in the pathobiology of cicatricial alopecias, and particularly, in FFA, which is currently considered as the most common type of primary lymphocytic scarring alopecia in the world. We envision that localized therapeutic inhibition of Cav1 in management of FFA (by cholesterol depleting agents, i.e., cyclodextrins/statins), could inhibit and potentially reverse bulge IP collapse and pathological EMT. Moreover, manipulation of HF Cav1 expression/localization would not only be relevant for management of cicatricial alopecia, but FFA could also serve as a model disease for elucidating the role of Cav1 in other stem cell-and/or IP collapse-related pathologies.

Original languageEnglish (US)
Article number572
JournalBiomedicines
Volume9
Issue number5
DOIs
StatePublished - May 2021
Externally publishedYes

Keywords

  • Caveolin-1
  • Cicatricial alopecia
  • Cyclodextrin
  • Frontal fibrosing alopecia
  • Hair follicle
  • Immune privilege
  • Statin

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)

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