Affiliation:
1. Department of Dermatology, Dongguk University Ilsan Hospital, 814 Siksa-dong, Ilsandong-gu, Goyang-si 10326, Republic of Korea
2. College of Pharmacy, Dongguk University, Seoul 04620, Republic of Korea
Abstract
Primary cilia play a significant role in influencing cell fate, including apoptosis in multiple cell types. In the lesional epidermis of vitiligo patients, a reduced number of ciliated cells was observed. Our study also revealed a downregulation of oral–facial digital syndrome type 1 (OFD1) in the affected skin of vitiligo patients. However, it remains unknown whether primary cilia are involved in the control of melanocyte apoptosis. While both intraflagellar transport 88 (IFT88) and retinitis pigmentosa GTPase regulator-interacting protein-1 like (RPGRIP1L) are associated with ciliogenesis in melanocytes, only the knockdown of OFD1, but not IFT88 and RPGRIP1L, resulted in increased melanocyte apoptosis. OFD1 knockdown led to a decrease in the expression of proteins involved in cell–extracellular matrix (ECM) interactions, including paxillin. The OFD1 amino acid residues 601-1012 interacted with paxillin, while the amino acid residues 1-601 were associated with ciliogenesis, suggesting that the OFD1 domains responsible for paxillin binding are distinct from those involved in ciliogenesis. OFD1 knockdown, but not IFT88 knockdown, inhibited melanocyte adhesion to the ECM, a defect that was restored by paxillin overexpression. In summary, our findings indicate that the downregulation of OFD1 induces melanocyte apoptosis, independent of any impairment in ciliogenesis, by reducing melanocyte adhesion to the ECM via paxillin.
Funder
National Research Foundation of Korea
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis
Reference46 articles.
1. Saif, G.A.B., Alshammary, A.F., and Ali Khan, I. (2023). Evaluation of CAT Variants A-89T, C389T, and C419T in Patients with Vitiligo in the Saudi Population. Medicina, 59.
2. Vitiligo: Interplay between oxidative stress and immune system;Laddha;Exp. Dermatol.,2013
3. Scrutinizing ciliopathies by unraveling ciliary interaction networks;Arts;Hum. Mol. Genet.,2011
4. Primary cilia and kidney injury: Current research status and future perspectives;Wang;Am. J. Physiol.-Ren. Physiol.,2013
5. The primary cilium: Guardian of organ development and homeostasis;Fry;Organogenesis,2014