BACKGROUND: Expression of transforming growth factor (TGF)-β1 and increases in angiogenesis and deposition of extracellular matrix are the key features of tracheal granulation formation. The aim of this study was to investigate the potential role of thalidomide in preventing granulation tissue formation from the aspect of cellular effects in vitro, including fibroblast proliferation, vascular endothelial growth factor (VEGF) release, and collagen production. METHODS: Human lung fibroblasts were obtained from bronchus and cultured. The effects of thalidomide on cell proliferation, migration, TGF-β1-induced VEGF, and signal pathway were investigated. RESULTS: Thalidomide (20 μM) not only inhibited cell proliferation after 24 h [fold increase of cell number, 0.85 ± 0.09 vs. 1.47 ± 0.14 (treatment vs. control group); P < 0.01] and 48 h of incubation (0.85 ± 0.10 vs. 1.97 ± 0.12; P < 0.001), it also inhibited cell migration and slowed wound closure at 24 h (P < 0.001). Thalidomide significantly attenuated TGF-β1-induced VEGF expression at both the mRNA and protein levels. Incubation of thalidomide with cells stimulated with TGF-β1 significantly inhibited their production of collagen. Thalidomide inhibited Smad3, STAT3, and subsequent p44/42 kinase phosphorylation. CONCLUSION: Thalidomide may inhibit human fibroblast proliferation and it is worthy of further in vivo investigation.
BACKGROUND: Expression of transforming growth factor (TGF)-β1 and increases in angiogenesis and deposition of extracellular matrix are the key features of tracheal granulation formation. The aim of this study was to investigate the potential role of thalidomide in preventing granulation tissue formation from the aspect of cellular effects in vitro, including fibroblast proliferation, vascular endothelial growth factor (VEGF) release, and collagen production. METHODS:Human lung fibroblasts were obtained from bronchus and cultured. The effects of thalidomide on cell proliferation, migration, TGF-β1-induced VEGF, and signal pathway were investigated. RESULTS:Thalidomide (20 μM) not only inhibited cell proliferation after 24 h [fold increase of cell number, 0.85 ± 0.09 vs. 1.47 ± 0.14 (treatment vs. control group); P < 0.01] and 48 h of incubation (0.85 ± 0.10 vs. 1.97 ± 0.12; P < 0.001), it also inhibited cell migration and slowed wound closure at 24 h (P < 0.001). Thalidomide significantly attenuated TGF-β1-induced VEGF expression at both the mRNA and protein levels. Incubation of thalidomide with cells stimulated with TGF-β1 significantly inhibited their production of collagen. Thalidomide inhibited Smad3, STAT3, and subsequent p44/42 kinase phosphorylation. CONCLUSION:Thalidomide may inhibit human fibroblast proliferation and it is worthy of further in vivo investigation.
Authors: G S Ashcroft; X Yang; A B Glick; M Weinstein; J L Letterio; D E Mizel; M Anzano; T Greenwell-Wild; S M Wahl; C Deng; A B Roberts Journal: Nat Cell Biol Date: 1999-09 Impact factor: 28.824
Authors: Guilian Niu; Kenneth L Wright; Mei Huang; Lanxi Song; Eric Haura; James Turkson; Shumin Zhang; Tianhong Wang; Dominic Sinibaldi; Domenico Coppola; Richard Heller; Lee M Ellis; James Karras; Jacqueline Bromberg; Drew Pardoll; Richard Jove; Hua Yu Journal: Oncogene Date: 2002-03-27 Impact factor: 9.867
Authors: Mona G Elhadidy; Ahlam Elmasry; Hassan Reda Hassan Elsayed; Mohammad El-Nablaway; Shereen Hamed; Mahmoud M Elalfy; Mohammed R Rabei Journal: Heliyon Date: 2021-10-13