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Hypoxia-Induced Collagen Synthesis of Human Lung Fibroblasts by Activating the Angiotensin System
Department of Respiratory Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
Institute of Clinical Medicine Renmin Hospital, Hubei University of Medicine, Shiyan 442000, Hubei, China
Department of Cardiology, Renmin Hospital, Hubei University of Medicine, Shiyan 442000, Hubei, China
Key Lab of Human Embryonic Stem Cell of Hubei Province, Department of Physiology, Hubei University of Medicine, Shiyan 442000, Hubei, China
Department of Respiratory Medicine, Fengtai Teaching Hospital, Capital Medical University, Beijing 100071, China
* Authors to whom correspondence should be addressed.
Received: 23 September 2013; in revised form: 21 November 2013 / Accepted: 25 November 2013 / Published: 10 December 2013
Abstract: The exact molecular mechanism that mediates hypoxia-induced pulmonary fibrosis needs to be further clarified. The aim of this study was to explore the effect and underlying mechanism of angiotensin II (Ang II) on collagen synthesis in hypoxic human lung fibroblast (HLF) cells. The HLF-1 cell line was used for in vitro studies. Angiotensinogen (AGT), angiotensin converting enzyme (ACE), angiotensin II type 1 receptor (AT1R) and angiotensin II type 2 receptor (AT2R) expression levels in human lung fibroblasts were analysed using real-time polymerase chain reaction (RT-PCR) after hypoxic treatment. Additionally, the collagen type I (Col-I), AT1R and nuclear factor κappaB (NF-κB) protein expression levels were detected using Western blot analysis, and NF-κB nuclear translocation was measured using immunofluorescence localization analysis. Ang II levels in HLF-1 cells were measured with an enzyme-linked immunosorbent assay (ELISA). We found that hypoxia increased Col-I mRNA and protein expression in HLF-1 cells, and this effect could be inhibited by an AT1R or AT2R inhibitor. The levels of NF-κB, RAS components and Ang II production in HLF-1 cells were significantly increased after the hypoxia exposure. Hypoxia or Ang II increased NF-κB-p50 protein expression in HLF-1 cells, and the special effect could be inhibited by telmisartan (TST), an AT1R inhibitor, and partially inhibited by PD123319, an AT2R inhibitor. Importantly, hypoxia-induced NF-κB nuclear translocation could be nearly completely inhibited by an AT1R or AT2R inhibitor. Furthermore pyrrolidine dithiocarbamate (PDTC), a NF-κB blocker, abolished the expression of hypoxia-induced AT1R and Col-I in HLF-1 cells. Our results indicate that Ang II-mediated NF-κB signalling via ATR is involved in hypoxia-induced collagen synthesis in human lung fibroblasts.
Keywords: angiotensin II; hypoxic HLF-1; collagen synthesis; nuclear factor κappaB
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MDPI and ACS Style
Liu, S.-S.; Wang, H.-Y.; Tang, J.-M.; Zhou, X.-M. Hypoxia-Induced Collagen Synthesis of Human Lung Fibroblasts by Activating the Angiotensin System. Int. J. Mol. Sci. 2013, 14, 24029-24045.
Liu S-S, Wang H-Y, Tang J-M, Zhou X-M. Hypoxia-Induced Collagen Synthesis of Human Lung Fibroblasts by Activating the Angiotensin System. International Journal of Molecular Sciences. 2013; 14(12):24029-24045.
Liu, Shan-Shan; Wang, Hao-Yan; Tang, Jun-Ming; Zhou, Xiu-Mei. 2013. "Hypoxia-Induced Collagen Synthesis of Human Lung Fibroblasts by Activating the Angiotensin System." Int. J. Mol. Sci. 14, no. 12: 24029-24045.