The Role of Adipsin, Complement Factor D, in the Pathogenesis of Graves' Orbitopathy.

Autor:	Byeon HJ; Department of Ophthalmology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea., Chae MK; Department of Ophthalmology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea., Ko J; Department of Ophthalmology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea., Lee EJ; Department of Endocrinology, Severance Hospital, Institute of Endocrine Research, Yonsei University College of Medicine, Seoul, Korea., Kikkawa DO; Division of Oculofacial Plastic and Reconstructive Surgery, Department of Ophthalmology, Shiley Eye Institute, University of California San Diego, La Jolla, California, United States., Jang SY; Department of Ophthalmology, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon, Korea., Yoon JS; Department of Ophthalmology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
Jazyk:	angličtina
Zdroj:	Investigative ophthalmology & visual science [Invest Ophthalmol Vis Sci] 2023 Aug 01; Vol. 64 (11), pp. 13.
DOI:	10.1167/iovs.64.11.13
Abstrakt:	Purpose: Graves' orbitopathy (GO) is an orbital manifestation of autoimmune Graves' disease, and orbital fibroblast is considered a target cell, producing pro-inflammatory cytokines and/or differentiating into adipocytes. Adipose tissue has been focused on as an endocrine and inflammatory organ secreting adipokines. We investigated the pathogenic role of a specific adipokine, adipsin, known as complement factor D in Graves' orbital fibroblasts. Methods: The messenger RNA (mRNA) expression of multiple adipokines was investigated in adipose tissues harvested from GO and healthy subjects. Adipsin protein production was analyzed in primary cultured orbital fibroblasts under insulin growth factor (IGF)-1, CD40 ligand (CD40L) stimulation, and adipogenesis. The effect of blocking adipsin with small interfering RNA (siRNA) on pro-inflammatory cytokine production and adipogenesis was evaluated using quantitative real-time PCR, Western blot, and ELISA. Adipogenic differentiation was identified using Oil Red O staining. Results: Adipsin gene expression was significantly elevated in GO tissue and increased after the stimulation of IGF-1 and CD40L, as well as adipocyte differentiation in GO cells. Silencing of adipsin suppressed IGF-1-induced IL-6, IL-8, COX2, ICAM-1, CCL2 gene expression, and IL-6 protein secretion. Adipsin suppression also attenuated adipocyte differentiation. Exogenous treatment of recombinant adipsin resulted in the activation of the Akt, ERK, p-38, and JNK signaling pathways. Conclusions: Adipsin, secreted by orbital fibroblasts, may play a distinct role in the pathogenesis of GO. Inhibition of adipsin ameliorated the production of pro-inflammatory cytokines and adipogenesis in orbital fibroblasts. Our study provides an in vitro basis suggesting adipsin as a potential therapeutic target for GO treatment.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu