Transforming growth factor-β1 suppress pentraxin-3 in human orbital fibroblasts

Purpose Transforming growth factor-beta (TGF-beta), 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-beta 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-beta 1 was exerted as an intervention and the expression of PTX3 was detected. To uncover the underlying mechanism, specific inhibitors of TGF-beta and siRNA knockdown of Smads were utilized. Results We found that TGF-beta 1 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-beta 1. Interestingly, the basic level of PTX3 and the magnitude of suppression were not significantly different between TAO and control groups. Furthermore, the TGF-beta 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-beta 1 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.