title: TWEAK/Fn14 promotes the proliferation and collagen synthesis of rat cardiac fibroblasts via the NF-кB pathway.
abstract: We wished to elucidate a potential role of the tumor necrosis factor-like weak inducer of apoptosis (TWEAK)/fibroblast growth factor-inducible molecule 14 (Fn14) axis in myocardial fibrosis. Stimulation of neonatal rat cardiac fibroblasts (CFs) with TWEAK could increase CFs numbers and collagen synthesis. Conversely, when CFs were pretreated with siRNA against Fn14, induction of cell proliferation and collagen synthesis by TWEAK were inhibited. Pretreatment with TWEAK on CFs induced activation of the nuclear factor-kappaB (NF-кB) pathway and subsequently increased the production of metalloproteinase-9 (MMP-9). Cell treatment with siRNA against Fn14 led to inhibition of the NF-кB pathway. Additionally, after stimulation of cell with ammonium pyrrolidine dithiocarbamate, cell proliferation and collagen synthesis induced by NF-кB and the upregulation of MMP-9 production were inhibited. The present study suggested that the TWEAK/Fn14 axis increased cell proliferation and collagen synthesis by activating the NF-кB pathway and increasing MMP-9 activity. This axis may be important for regulating myocardial fibrosis.
authors.affiliation: Department of Cardiology, Second Hospital of Shandong University, 247 Beiyuan Street, Jinan 250033, China.
authors.forename: Hui-Na
authors.initials: HN
authors.lastname: Chen
authors.forename: De-Jin
authors.initials: DJ
authors.lastname: Wang
authors.forename: Man-Yi
authors.initials: MY
authors.lastname: Ren
authors.forename: Qi-Lei
authors.initials: QL
authors.lastname: Wang
authors.forename: Shu-Jian
authors.initials: SJ
authors.lastname: Sui
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D049109:Cell Proliferation; D003094:Collagen / Q000096:biosynthesis* / Q000235:genetics; D000074049:Cytokine TWEAK; D005347:Fibroblasts / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D008565:Membrane Proteins / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D015398:Signal Transduction; D000074050:TWEAK Receptor; D048069:Tumor Necrosis Factors / Q000378:metabolism*
chemical_list: D051017:Apoptosis Regulatory Proteins; D000074049:Cytokine TWEAK; D008565:Membrane Proteins; D016328:NF-kappa B; D012333:RNA, Messenger; D018124:Receptors, Tumor Necrosis Factor; D000074050:TWEAK Receptor; C000613300:Tnfrsf12a protein, rat; C497771:Tnfsf12 protein, rat; D048069:Tumor Necrosis Factors; D003094:Collagen; D020780:Matrix Metalloproteinase 9