Intratracheal gene transfer of tissue factor pathway inhibitor attenuates pulmonary fibrosis

Kijiyama, Naoki; Ueno, Hikaru; Sugimoto, Isamu; Sasaguri, Yasuyuki; Yatera, Kazuhiro; Kido, Masamitsu; Gabazza, Esteban C.; Suzuki, Koji; Hashimoto, Eikichi; Takeya, Hiroyuki

doi:10.1016/j.bbrc.2005.11.127

Cited by 32 publications

(19 citation statements)

References 38 publications

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“…Typically fibrotic tissue contains increased concentrations of collagen, a rich blood supply and activated fibroblasts, as identified by a-SMA. Several groups have shown the attenuation of collagen production and deposition leads to reduced levels of pulmonary fibrosis (48)(49)(50)(51)(52). Following transcription, translation, and secretion, procollagen I assembles and is posttranslationally modified in the extracellular space to create an insoluble fibrotic matrix of collagen fibers.…”

Section: Discussionmentioning

confidence: 99%

LOX-Mediated Collagen Crosslinking Is Responsible for Fibrosis-Enhanced Metastasis

et al. 2013

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Tumor metastasis is a highly complex, dynamic, and inefficient process involving multiple steps, yet it accounts for more than 90% of cancer-related deaths. Although it has long been known that fibrotic signals enhance tumor progression and metastasis, the underlying molecular mechanisms are still unclear. Identifying events involved in creating environments that promote metastatic colonization and growth are critical for the development of effective cancer therapies. Here, we show a critical role for lysyl oxidase (LOX) in establishing a milieu within fibrosing tissues that is favorable to growth of metastastic tumor cells. We show that LOX-dependent collagen crosslinking is involved in creating a growth-permissive fibrotic microenvironment capable of supporting metastatic growth by enhancing tumor cell persistence and survival. We show that therapeutic targeting of LOX abrogates not only the extent to which fibrosis manifests, but also prevents fibrosis-enhanced metastatic colonization. Finally, we show that the LOXmediated collagen crosslinking directly increases tumor cell proliferation, enhancing metastatic colonization and growth manifesting in vivo as increased metastasis. This is the first time that crosslinking of collagen I has been shown to enhance metastatic growth. These findings provide an important link between ECM homeostasis, fibrosis, and cancer with important clinical implications for both the treatment of fibrotic disease and cancer. Cancer Res; 73(6);

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Section: Discussionmentioning

confidence: 99%

LOX-Mediated Collagen Crosslinking Is Responsible for Fibrosis-Enhanced Metastasis

et al. 2013

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“…), Angiotensin receptor blockers (Losartan (Fang, Zhu, Hu, & Liu, 2002;Marshall et al, 2004;Yao, Zhu, Zhao, & Lu, 2006), Candesartan (Otsuka, Takahashi, Shiratori, Chiba, & Abe, 2004), Valsartan (F. Liu, Xu, & Ye, 2005;Mancini & Khalil, 2005) etc. ), Anticoagulants (TFPI = tissue factor pathway inhibitor (Kijiyama et al, 2006), Urokinase (Hart, Whidden, Green, Henkin, & Woods, 1994;Hattori et al, 2004;Howell et al, 2001;Howell, Laurent, & Chambers, 2002;Ikeda, Hirose, Koto, Hirano, & Shigematsu, 1989), Heparin (Gunther et al, 2003;Piguet, Van, & Guo, 1996), APC = anticoagulant protein C (S. Shimizu et al, 2003;H. Yasui et al, 2001), Thromboxane synthetase inhibitor (Sato et al, 2004) etc.…”

Section: Drug Intervention Studies In the Bleomycin Modelmentioning

confidence: 99%

The bleomycin animal model: A useful tool to investigate treatment options for idiopathic pulmonary fibrosis?

Moeller

Ask

Warburton

et al. 2008

The International Journal of Biochemistry & Cell Biology

825

724

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Different animal models of pulmonary fibrosis have been developed to investigate potential therapies for idiopathic pulmonary fibrosis (IPF). The most common is the bleomycin model in rodents (mouse, rat and hamster). Over the years, numerous agents have been shown to inhibit fibrosis in this model. However, to date none of these compounds are used in the clinical management of IPF and none has shown a comparable antifibrotic effect in humans. We performed a systematic review of publications on drug efficacy studies in the bleomycin model to evaluate the value of this model regarding transferability to clinical use. Between 1980 and 2006 we identified 246 experimental studies describing beneficial antifibrotic compounds in the bleomycin model. In 221 of the studies we found enough details about the timing of drug application to allow inter-study comparison. 211 of those used a preventive regimen (drug given ≤ day 7 after last bleomycin application), only 10 were therapeutic trials (> 7 days after last bleomycin application). It is critical to distinguish between drugs interfering with the inflammatory and early fibrogenic response from those preventing progression of fibrosis, the latter likely much more meaningful for clinical application. All potential antifibrotic compounds should be evaluated in the phase of established fibrosis rather than in the early period of bleomycin-induced inflammation for assessment of its antifibrotic properties. Further care should be taken in extrapolation of drugs successfully tested in the bleomycin model due to partial reversibility of bleomycin induced fibrosis over time. The use of alternative and more robust animal models, which better reflect human IPF, is warranted.

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“…Targeting of the coagulation cascade in these models, using a variety of strategies such as direct thrombin inhibition [17], TFPI [18], intratracheal administration of activated protein C [19] and aerosolised heparin [20], led to a reduction in lung collagen accumulation and the development of fibrotic lesions. Fibrin acts as a provisional matrix for the recruitment of inflammatory cells and fibroblasts and recent evidence also suggests that the provisional ECM is a key regulator of EMT [8].…”

Section: The Coagulation Cascade In Pulmonary Fibrosismentioning

confidence: 99%

Abnormal wound healing responses in pulmonary fibrosis: focus on coagulation signalling

Chambers¹

2008

European Respiratory Review

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The normal response of tissue to injury involves a sequence of overlapping events, which need to occur in a timely and controlled manner for successful tissue repair and restoration of normal function. Failure to control the healing process can lead to considerable tissue remodelling and the replacement of functional tissue with permanent fibrous scar tissue.It is proposed that pulmonary fibrosis arises from repetitive, widespread epithelial injury. However, the nature of the insult for the most common and most fatal form of pulmonary fibrosis, idiopathic pulmonary fibrosis (IPF), is currently unknown and the pathogenetic pathways leading to IPF remain to be fully elucidated. Increasing evidence suggests that abnormalities in a number of pathways involved in the wound healing response may play central roles.The present article will briefly review the pathways involved in wound healing focusing on the control of fibroblast/myofibroblast function and the coagulation cascade acting via the family of signalling receptors, the proteinase activated receptors, which influence a range of cellular responses implicated in the development of pulmonary fibrosis.Understanding the involvement of these pathways in the aberrant wound repair-response in pulmonary fibrosis may lead to the identification of new targets and strategies for therapeutic intervention.

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Intratracheal gene transfer of tissue factor pathway inhibitor attenuates pulmonary fibrosis

Cited by 32 publications

References 38 publications

LOX-Mediated Collagen Crosslinking Is Responsible for Fibrosis-Enhanced Metastasis

LOX-Mediated Collagen Crosslinking Is Responsible for Fibrosis-Enhanced Metastasis

The bleomycin animal model: A useful tool to investigate treatment options for idiopathic pulmonary fibrosis?

Abnormal wound healing responses in pulmonary fibrosis: focus on coagulation signalling

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