title: TGFBR3, a potential negative regulator of TGF-β signaling, protects cardiac fibroblasts from hypoxia-induced apoptosis.
abstract: A lot of evidence indicates that cardiac fibroblasts are essential for maintaining the structure and function of heart. The present study examined whether TGFBR3 (transforming growth factor type III receptor, also known as betaglycan) could prevent hypoxia-induced injury in neonatal mice cardiac fibroblasts, if so, its possible molecular targets. MTT, electron microscopy and TUNEL assay were used to identify cell viability and apoptosis in neonatal mice cardiac fibroblasts. Results showed that hypoxia for 24 h markedly reduce cell viability by 49.8 ± 8.9%, largely via apoptosis. However, hypoxia-induced apoptosis in cardiac fibroblasts were almost completely prevented by overexpression of TGFBR3. In the present study, hypoxia also induced TGF-β1, p-Smad2/3 expression, TGFBR1-TGFBR2 complex formation and collagen production in cardiac fibroblasts, which were attenuated substantially by TGFBR3 overexpression. TGFBR3 also reversed Bax up-regulation, Bcl-2 down-regulation and Caspase-3 activation induced by hypoxia in cardiac fibroblasts. Hypoxia or TGF-β1 itself triggered an increase of [Ca(2+) ](i) in cardiac fibroblasts, which were both inhibited by TGFBR3 overexpression. Taken together, our results indicate that TGFBR3 may act as a protective factor in apoptotic process of cardiac fibroblasts by negative regulation of TGF-β signaling and represent a potential therapeutic target for heart remodeling after hypoxia injury.
authors.affiliation: Department of Pharmacology, The State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Harbin Medical University, Harbin, PR China.
authors.forename: Wenfeng
authors.initials: W
authors.lastname: Chu
authors.forename: Xiaoxue
authors.initials: X
authors.lastname: Li
authors.forename: Cui
authors.initials: C
authors.lastname: Li
authors.forename: Lin
authors.initials: L
authors.lastname: Wan
authors.forename: Hui
authors.initials: H
authors.lastname: Shi
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Song
authors.forename: Xingyuan
authors.initials: X
authors.lastname: Liu
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.forename: Chun
authors.initials: C
authors.lastname: Zhang
authors.forename: Hongli
authors.initials: H
authors.lastname: Shan
authors.forename: Yanjie
authors.initials: Y
authors.lastname: Lu
authors.forename: Baofeng
authors.initials: B
authors.lastname: Yang
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000502:physiology*; D015687:Cell Hypoxia / Q000235:genetics; D002478:Cells, Cultured; D015536:Down-Regulation / Q000235:genetics / Q000502:physiology*; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008815:Mice, Inbred Strains; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000378:metabolism / Q000473:pathology; D011509:Proteoglycans / Q000235:genetics / Q000502:physiology*; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors* / Q000502:physiology
chemical_list: D051017:Apoptosis Regulatory Proteins; D011509:Proteoglycans; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; C071736:betaglycan