Transforming growth factor-β1 suppress pentraxin-3 in human orbital fibroblasts
- 16 April 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Endocrine
- Vol. 70 (1), 78-84
- https://doi.org/10.1007/s12020-020-02307-3
Abstract
Purpose Transforming growth factor-β (TGF-β), recognized as a crucial factor in regulating fibrosis and tissue remodeling, plays a role in thyroid-associated ophthalmopathy (TAO). Pentraxin-3 (PTX3), a member of pentraxins, was recently implicated in many autoimmune and fibrotic diseases. Thus, we hypothesize if there is a potential correlation between TGF-β and PTX3 in orbital fibroblasts (OFs). Methods Several strains of OFs obtained from patients with TAO (n = 8) and healthy donors (n = 3) were established as the study model. Recombinant TGF-β1 was exerted as an intervention and the expression of PTX3 was detected. To uncover the underlying mechanism, specific inhibitors of TGF-β and siRNA knockdown of Smads were utilized. Results We found that TGF-β1 can reduce PTX3 protein expression in OFs. We also demonstrated that this downregulation was mediated at a pretranslational level, and PTX3 mRNA was inhibited in a time- and concentration-dependent manner by TGF-β1. Interestingly, the basic level of PTX3 and the magnitude of suppression were not significantly different between TAO and control groups. Furthermore, the TGF-β receptor complex (type I:type II) and the Smad2/3-Smad4-dependent pathway are essential for TGF-mediated PTX3 repression. Conclusion These findings indicated that TGF-β1 can inhibit PTX3 expression in human OFs, which may participate in inflammation and fibrosis in patients with TAO and provide a potential target for the antifibrotic treatment.Keywords
Funding Information
- National Natural Science Foundation of China (81770959, 81770959)
- Shanghai Municipal Population and Family Planning Commission (201640215)
This publication has 29 references indexed in Scilit:
- PTX3, a Humoral Pattern Recognition Molecule, in Innate Immunity, Tissue Repair, and CancerPhysiological Reviews, 2018
- TGF-β and the TGF-β Family: Context-Dependent Roles in Cell and Tissue PhysiologyCold Spring Harbor Perspectives in Biology, 2016
- Cell density-dependent stimulation of PAI-1 and hyaluronan synthesis by TGF-β in orbital fibroblastsJournal of Endocrinology, 2016
- Incorporation of Pentraxin 3 into Hyaluronan Matrices Is Tightly Regulated and Promotes Matrix Cross-linkingJournal of Biological Chemistry, 2014
- Pentraxin 3 Inhibits Acute Renal Injury-Induced Interstitial Fibrosis Through Suppression of IL-6/Stat3 PathwayInflammation, 2014
- Antifibrotic Effects of Quercetin in Primary Orbital Fibroblasts and Orbital Fat Tissue Cultures of Graves' OrbitopathyInvestigative Opthalmology & Visual Science, 2012
- Graves' OphthalmopathyNew England Journal of Medicine, 2010
- Expression of long pentraxin PTX3 in human adipose tissue and its relation with cardiovascular risk factorsAtherosclerosis, 2009
- TGF‐β induced hyaluronan synthesis in orbital fibroblasts involves protein kinase C βII activation in vitroJournal of Cellular Biochemistry, 2005
- TGF‐β signaling and the fibrotic responseThe FASEB Journal, 2004