Zhaoxing Dong1, Xinxiang Zhao2, Wenlin Tai3, Wen Lei4, Yin Wang5, ZhenKun Li6, Tao Zhang7. 1. Department of Respiratory, The 2nd Affiliated Hospital of Kunming Medical University; Kunming, Yunnan, China. Electronic address: dongkm@hotmail.com. 2. Department of Radiology, The 2nd Affiliated Hospital of Kunming Medical University; Kunming, Yunnan, China. Electronic address: zhaoxinxiang06@126.com. 3. Department of Clinical Laboratory, Yunnan Molecular Diagnostic Center, The 2nd Affiliated Hospital of Kunming Medical University, Dianmian Road, Kunming, Yunnan, China. Electronic address: 2820582685@qq.com. 4. Department of Respiratory, The 2nd Affiliated Hospital of Kunming Medical University; Kunming, Yunnan, China. Electronic address: 2233851218@qq.com. 5. Department of Respiratory, The 2nd Affiliated Hospital of Kunming Medical University; Kunming, Yunnan, China. Electronic address: w.y925@163.com. 6. Department of Respiratory, The 2nd Affiliated Hospital of Kunming Medical University; Kunming, Yunnan, China. Electronic address: ljk5718@sina.com.cn. 7. Department of Respiratory, The 2nd Affiliated Hospital of Kunming Medical University; Kunming, Yunnan, China. Electronic address: ZT6958@sina.com.cn.
Abstract
AIMS: Pulmonary fibrosis is a type of chronic lung disease and has characteristics that progress quickly, has a high fatality rate and a poor therapeutic effect. Our previous research showed that interleukin-27(IL-27) potentially attenuates BLM-induced pulmonary fibrosis, but the function of IL-27 in lung fibroblasts (LFs) differentiation pulmonary fibrosis is yet to be known. MAIN METHODS: Here we investigated the effect of IL-27 on the proliferation, differentiation and collagen synthesis of lung fibroblasts induced by transforming growth factor-β1 (TGF-β1)using MTT, bromodeoxyuridine(BrdU) staining, real-time quantitative PCR(qPCR), Western blot, cell cycle FACS assay and immunofluorescence. We also examined the expression of the JAK/STAT and TGF-β1/Smad signaling pathway of IL-27 in lung fibroblasts. KEY FINDINGS: TGF-β1 treated lung fibroblasts showed significantly increased proliferation, differentiation and collagen synthesis as well as overactivated JAK/STAT and TGF-β1/Smad signaling. However, the presence of IL-27 weakened these effects and obviously inactivated the JAK/STAT and TGF-β1/Smad signaling pathways. SIGNIFICANCE: Our results indicate that IL-27 may play an anti-fibrotic role in the development, differentiation and collagen synthesis in lung fibroblasts. These data also may provide a target gene therapy method in treating pulmonary fibrosis.
AIMS: Pulmonary fibrosis is a type of chronic lung disease and has characteristics that progress quickly, has a high fatality rate and a poor therapeutic effect. Our previous research showed that interleukin-27(IL-27) potentially attenuates BLM-induced pulmonary fibrosis, but the function of IL-27 in lung fibroblasts (LFs) differentiation pulmonary fibrosis is yet to be known. MAIN METHODS: Here we investigated the effect of IL-27 on the proliferation, differentiation and collagen synthesis of lung fibroblasts induced by transforming growth factor-β1 (TGF-β1)using MTT, bromodeoxyuridine(BrdU) staining, real-time quantitative PCR(qPCR), Western blot, cell cycle FACS assay and immunofluorescence. We also examined the expression of the JAK/STAT and TGF-β1/Smad signaling pathway of IL-27 in lung fibroblasts. KEY FINDINGS: TGF-β1 treated lung fibroblasts showed significantly increased proliferation, differentiation and collagen synthesis as well as overactivated JAK/STAT and TGF-β1/Smad signaling. However, the presence of IL-27 weakened these effects and obviously inactivated the JAK/STAT and TGF-β1/Smad signaling pathways. SIGNIFICANCE: Our results indicate that IL-27 may play an anti-fibrotic role in the development, differentiation and collagen synthesis in lung fibroblasts. These data also may provide a target gene therapy method in treating pulmonary fibrosis.
Authors: Alex Zhavoronkov; Evgeny Izumchenko; Riya R Kanherkar; Mahder Teka; Charles Cantor; Kebreten Manaye; David Sidransky; Michael D West; Eugene Makarev; Antonei Benjamin Csoka Journal: Cell Cycle Date: 2016-06-17 Impact factor: 4.534