Transforming growth factor-ß1 suppress pentraxin-3 in human orbital fibroblasts.

ABSTRACT

PURPOSE: Transforming growth factor-ß (TGF-ß), 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-ß 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-ß1 was exerted as an intervention and the expression of PTX3 was detected. To uncover the underlying mechanism, specific inhibitors of TGF-ß and siRNA knockdown of Smads were utilized. RESULTS: We found that TGF-ß1 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-ß1. Interestingly, the basic level of PTX3 and the magnitude of suppression were not significantly different between TAO and control groups. Furthermore, the TGF-ß receptor complex (type Itype II) and the Smad2/3-Smad4-dependent pathway are essential for TGF-mediated PTX3 repression. CONCLUSION: These findings indicated that TGF-ß1 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.