Jiale Diao1, Xinxin Chen1, Lihong Jiang2, Pei Mou1, Ruili Wei3. 1. Department of Ophthalmology, Changzheng Hospital of Naval Medicine University, 415 Fengyang Road, Huangpu District, Shanghai, 200003, China. 2. Department of Ophthalmology, Zhabei Central Hospital, Jingan District, 619 Zhonghua Xin Road, Shanghai, 200070, China. 3. Department of Ophthalmology, Changzheng Hospital of Naval Medicine University, 415 Fengyang Road, Huangpu District, Shanghai, 200003, China. ruiliwei@126.com.
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.
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.
Entities:
Keywords:
Fibrosis; Orbital fibroblast; Pentraxin-3; Thyroid-associated ophthalmopathy; Transforming growth factor-β1
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