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

Authors
 Hyeong Ju Byeon  ;  Min Kyung Chae  ;  JaeSang Ko  ;  Eun Jig Lee  ;  Don O Kikkawa  ;  Sun Young Jang  ;  Jin Sook Yoon 
Citation
 INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, Vol.64(11) : 13, 2023-08 
Journal Title
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
ISSN
 0146-0404 
Issue Date
2023-08
MeSH
Adipogenesis ; Adipokines / metabolism ; CD40 Ligand ; Cells, Cultured ; Complement Factor D* / genetics ; Cytokines / metabolism ; Fibroblasts / metabolism ; Graves Ophthalmopathy* / metabolism ; Humans ; Insulin-Like Growth Factor I / metabolism ; Interleukin-6 / metabolism ; Orbit / metabolism
Abstract
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.
Files in This Item:
T202304791.pdf Download
DOI
10.1167/iovs.64.11.13
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Ophthalmology (안과학교실) > 1. Journal Papers
Yonsei Authors
Ko, Jaesang(고재상) ORCID logo https://orcid.org/0000-0002-3011-7213
Byeon, Hyeong Ju(변형주) ORCID logo https://orcid.org/0000-0003-0285-0175
Yoon, Jin Sook(윤진숙) ORCID logo https://orcid.org/0000-0002-8751-9467
Lee, Eun Jig(이은직) ORCID logo https://orcid.org/0000-0002-9876-8370
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/196237
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