Cargando…

Adiponectin Promotes VEGF Expression in Rheumatoid Arthritis Synovial Fibroblasts and Induces Endothelial Progenitor Cell Angiogenesis by Inhibiting miR-106a-5p

Rheumatoid arthritis (RA) is an erosive polyarthritis that can lead to severe joint destruction and painful disability if left untreated. Angiogenesis, a critical pathogenic mechanism in RA, attracts inflammatory leukocytes into the synovium, which promotes production of proinflammatory cytokines an...

Descripción completa

Detalles Bibliográficos
Autores principales: Huang, Chien-Chung, Law, Yat-Yin, Liu, Shan-Chi, Hu, Sung-Lin, Lin, Jun-An, Chen, Chao-Ju, Wang, Shih-Wei, Tang, Chih-Hsin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8534315/
https://www.ncbi.nlm.nih.gov/pubmed/34685605
http://dx.doi.org/10.3390/cells10102627
_version_ 1784587523250454528
author Huang, Chien-Chung
Law, Yat-Yin
Liu, Shan-Chi
Hu, Sung-Lin
Lin, Jun-An
Chen, Chao-Ju
Wang, Shih-Wei
Tang, Chih-Hsin
author_facet Huang, Chien-Chung
Law, Yat-Yin
Liu, Shan-Chi
Hu, Sung-Lin
Lin, Jun-An
Chen, Chao-Ju
Wang, Shih-Wei
Tang, Chih-Hsin
author_sort Huang, Chien-Chung
collection PubMed
description Rheumatoid arthritis (RA) is an erosive polyarthritis that can lead to severe joint destruction and painful disability if left untreated. Angiogenesis, a critical pathogenic mechanism in RA, attracts inflammatory leukocytes into the synovium, which promotes production of proinflammatory cytokines and destructive proteases. Adipokines, inflammatory mediators secreted by adipose tissue, also contribute to the pathophysiology of RA. The most abundant serum adipokine is adiponectin, which demonstrates proinflammatory effects in RA, although the mechanisms linking adiponectin and angiogenic manifestations of RA are not well understood. Our investigations with the human MH7A synovial cell line have revealed that adiponectin dose- and time-dependently increases vascular endothelial growth factor (VEGF) expression, stimulating endothelial progenitor cell (EPC) tube formation and migration. These adiponectin-induced angiogenic activities were facilitated by MEK/ERK signaling. In vivo experiments confirmed adiponectin-induced downregulation of microRNA-106a-5p (miR-106a-5p). Inhibiting adiponectin reduced joint swelling, bone destruction, and angiogenic marker expression in collagen-induced arthritis (CIA) mice. Our evidence suggests that targeting adiponectin has therapeutic potential for patients with RA. Clinical investigations are needed.
format Online
Article
Text
id pubmed-8534315
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-85343152021-10-23 Adiponectin Promotes VEGF Expression in Rheumatoid Arthritis Synovial Fibroblasts and Induces Endothelial Progenitor Cell Angiogenesis by Inhibiting miR-106a-5p Huang, Chien-Chung Law, Yat-Yin Liu, Shan-Chi Hu, Sung-Lin Lin, Jun-An Chen, Chao-Ju Wang, Shih-Wei Tang, Chih-Hsin Cells Article Rheumatoid arthritis (RA) is an erosive polyarthritis that can lead to severe joint destruction and painful disability if left untreated. Angiogenesis, a critical pathogenic mechanism in RA, attracts inflammatory leukocytes into the synovium, which promotes production of proinflammatory cytokines and destructive proteases. Adipokines, inflammatory mediators secreted by adipose tissue, also contribute to the pathophysiology of RA. The most abundant serum adipokine is adiponectin, which demonstrates proinflammatory effects in RA, although the mechanisms linking adiponectin and angiogenic manifestations of RA are not well understood. Our investigations with the human MH7A synovial cell line have revealed that adiponectin dose- and time-dependently increases vascular endothelial growth factor (VEGF) expression, stimulating endothelial progenitor cell (EPC) tube formation and migration. These adiponectin-induced angiogenic activities were facilitated by MEK/ERK signaling. In vivo experiments confirmed adiponectin-induced downregulation of microRNA-106a-5p (miR-106a-5p). Inhibiting adiponectin reduced joint swelling, bone destruction, and angiogenic marker expression in collagen-induced arthritis (CIA) mice. Our evidence suggests that targeting adiponectin has therapeutic potential for patients with RA. Clinical investigations are needed. MDPI 2021-10-01 /pmc/articles/PMC8534315/ /pubmed/34685605 http://dx.doi.org/10.3390/cells10102627 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Huang, Chien-Chung
Law, Yat-Yin
Liu, Shan-Chi
Hu, Sung-Lin
Lin, Jun-An
Chen, Chao-Ju
Wang, Shih-Wei
Tang, Chih-Hsin
Adiponectin Promotes VEGF Expression in Rheumatoid Arthritis Synovial Fibroblasts and Induces Endothelial Progenitor Cell Angiogenesis by Inhibiting miR-106a-5p
title Adiponectin Promotes VEGF Expression in Rheumatoid Arthritis Synovial Fibroblasts and Induces Endothelial Progenitor Cell Angiogenesis by Inhibiting miR-106a-5p
title_full Adiponectin Promotes VEGF Expression in Rheumatoid Arthritis Synovial Fibroblasts and Induces Endothelial Progenitor Cell Angiogenesis by Inhibiting miR-106a-5p
title_fullStr Adiponectin Promotes VEGF Expression in Rheumatoid Arthritis Synovial Fibroblasts and Induces Endothelial Progenitor Cell Angiogenesis by Inhibiting miR-106a-5p
title_full_unstemmed Adiponectin Promotes VEGF Expression in Rheumatoid Arthritis Synovial Fibroblasts and Induces Endothelial Progenitor Cell Angiogenesis by Inhibiting miR-106a-5p
title_short Adiponectin Promotes VEGF Expression in Rheumatoid Arthritis Synovial Fibroblasts and Induces Endothelial Progenitor Cell Angiogenesis by Inhibiting miR-106a-5p
title_sort adiponectin promotes vegf expression in rheumatoid arthritis synovial fibroblasts and induces endothelial progenitor cell angiogenesis by inhibiting mir-106a-5p
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8534315/
https://www.ncbi.nlm.nih.gov/pubmed/34685605
http://dx.doi.org/10.3390/cells10102627
work_keys_str_mv AT huangchienchung adiponectinpromotesvegfexpressioninrheumatoidarthritissynovialfibroblastsandinducesendothelialprogenitorcellangiogenesisbyinhibitingmir106a5p
AT lawyatyin adiponectinpromotesvegfexpressioninrheumatoidarthritissynovialfibroblastsandinducesendothelialprogenitorcellangiogenesisbyinhibitingmir106a5p
AT liushanchi adiponectinpromotesvegfexpressioninrheumatoidarthritissynovialfibroblastsandinducesendothelialprogenitorcellangiogenesisbyinhibitingmir106a5p
AT husunglin adiponectinpromotesvegfexpressioninrheumatoidarthritissynovialfibroblastsandinducesendothelialprogenitorcellangiogenesisbyinhibitingmir106a5p
AT linjunan adiponectinpromotesvegfexpressioninrheumatoidarthritissynovialfibroblastsandinducesendothelialprogenitorcellangiogenesisbyinhibitingmir106a5p
AT chenchaoju adiponectinpromotesvegfexpressioninrheumatoidarthritissynovialfibroblastsandinducesendothelialprogenitorcellangiogenesisbyinhibitingmir106a5p
AT wangshihwei adiponectinpromotesvegfexpressioninrheumatoidarthritissynovialfibroblastsandinducesendothelialprogenitorcellangiogenesisbyinhibitingmir106a5p
AT tangchihhsin adiponectinpromotesvegfexpressioninrheumatoidarthritissynovialfibroblastsandinducesendothelialprogenitorcellangiogenesisbyinhibitingmir106a5p