Next Article in Journal
Idiosyncratic Drug-Induced Liver Injury: Mechanistic and Clinical Challenges
Previous Article in Journal
MicroRNAs, Parkinson’s Disease, and Diabetes Mellitus
 
 
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Article

JNK and p38 Inhibitors Prevent Transforming Growth Factor-β1-Induced Myofibroblast Transdifferentiation in Human Graves’ Orbital Fibroblasts

1
Department of Ophthalmology, Taipei Veterans General Hospital, Taipei 112, Taiwan
2
School of Medicine, National Yang Ming University, Taipei 112, Taiwan
3
School of Medicine, National Yang Ming Chiao Tung University, Hsinchu 30010, Taiwan
4
Biomedical Commercialization Center, Taipei Medical University, Taipei 110, Taiwan
5
Department of Ophthalmology, Koo Foundation Sun Yat-Sen Cancer Center, Taipei 112, Taiwan
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2021, 22(6), 2952; https://doi.org/10.3390/ijms22062952
Submission received: 6 February 2021 / Revised: 8 March 2021 / Accepted: 12 March 2021 / Published: 14 March 2021
(This article belongs to the Section Molecular Endocrinology and Metabolism)

Abstract

Transforming growth factor-β1 (TGF-β1)-induced myofibroblast transdifferentiation from orbital fibroblasts is known to dominate tissue remodeling and fibrosis in Graves’ ophthalmopathy (GO). However, the signaling pathways through which TGF-β1 activates Graves’ orbital fibroblasts remain unclear. This study investigated the role of the mitogen-activated protein kinase (MAPK) pathway in TGF-β1-induced myofibroblast transdifferentiation in human Graves’ orbital fibroblasts. The MAPK pathway was assessed by measuring the phosphorylation of p38, c-Jun N-terminal kinase (JNK), and extracellular-signal-regulated kinase (ERK) by Western blots. The expression of connective tissue growth factor (CTGF), α-smooth muscle actin (α-SMA), and fibronectin representing fibrogenesis was estimated. The activities of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) responsible for extracellular matrix (ECM) metabolism were analyzed. Specific pharmacologic kinase inhibitors were used to confirm the involvement of the MAPK pathway. After treatment with TGF-β1, the phosphorylation levels of p38 and JNK, but not ERK, were increased. CTGF, α-SMA, and fibronectin, as well as TIMP-1 and TIMP-3, were upregulated, whereas the activities of MMP-2/-9 were inhibited. The effects of TGF-β1 on the expression of these factors were eliminated by p38 and JNK inhibitors. The results suggested that TGF-β1 could induce myofibroblast transdifferentiation in human Graves’ orbital fibroblasts through the p38 and JNK pathways.
Keywords: c-Jun N-terminal kinase; Graves’ orbital fibroblasts; Graves’ ophthalmopathy; mitogen-activated protein kinase; p38; transforming growth factor-β1 c-Jun N-terminal kinase; Graves’ orbital fibroblasts; Graves’ ophthalmopathy; mitogen-activated protein kinase; p38; transforming growth factor-β1

Share and Cite

MDPI and ACS Style

Hou, T.-Y.; Wu, S.-B.; Kau, H.-C.; Tsai, C.-C. JNK and p38 Inhibitors Prevent Transforming Growth Factor-β1-Induced Myofibroblast Transdifferentiation in Human Graves’ Orbital Fibroblasts. Int. J. Mol. Sci. 2021, 22, 2952. https://doi.org/10.3390/ijms22062952

AMA Style

Hou T-Y, Wu S-B, Kau H-C, Tsai C-C. JNK and p38 Inhibitors Prevent Transforming Growth Factor-β1-Induced Myofibroblast Transdifferentiation in Human Graves’ Orbital Fibroblasts. International Journal of Molecular Sciences. 2021; 22(6):2952. https://doi.org/10.3390/ijms22062952

Chicago/Turabian Style

Hou, Tzu-Yu, Shi-Bei Wu, Hui-Chuan Kau, and Chieh-Chih Tsai. 2021. "JNK and p38 Inhibitors Prevent Transforming Growth Factor-β1-Induced Myofibroblast Transdifferentiation in Human Graves’ Orbital Fibroblasts" International Journal of Molecular Sciences 22, no. 6: 2952. https://doi.org/10.3390/ijms22062952

APA Style

Hou, T.-Y., Wu, S.-B., Kau, H.-C., & Tsai, C.-C. (2021). JNK and p38 Inhibitors Prevent Transforming Growth Factor-β1-Induced Myofibroblast Transdifferentiation in Human Graves’ Orbital Fibroblasts. International Journal of Molecular Sciences, 22(6), 2952. https://doi.org/10.3390/ijms22062952

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop