Increased serum levels of endostatin in patients with idiopathic pulmonary fibrosis

Sumi, Masahiro; Satoh, Hiroaki; Kagohashi, Katsunori; Ishikawa, Hiroichi; Sekizawa, Kiyohisa

doi:10.1002/jcla.20069

Cited by 25 publications

(15 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Elevated levels of serum and BALF endostatin are seen in fibrotic disorders such as IPF and SSc (16–18). Endostatin was increased in IPF patients with severe respiratory dysfunction and in SSc patients with pulmonary fibrosis and severe skin fibrosis compared to patients without those clinical manifestations (16–18).…”

Section: Discussionmentioning

confidence: 99%

“…Recent studies have shown that endostatin is 2 to 20 times higher in serum and/or bronchoalveolar lavage fluid (BALF) from patients with idiopathic pulmonary fibrosis (IPF) and SSc-associated pulmonary fibrosis than from normal subjects (16–18). Because cytokines and signaling molecules implicated in angiogenesis development have also been identified in purpose, we evaluated the effect of endostatin and endostatin-derived peptides on the generation of fibrosis in vitro using primary human fibroblasts, ex vivo using human skin, and in vivo in TGF-β– and bleomycin-induced dermal and pulmonary fibrosis.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

A Peptide Derived from Endostatin Ameliorates Organ Fibrosis

et al. 2012

View full text Add to dashboard Cite

Fibroproliferative disorders such as idiopathic pulmonary fibrosis and systemic sclerosis have no effective therapies and result in significant morbidity and mortality due to progressive organ fibrosis. We examined the effect of peptides derived from endostatin on existing fibrosis and fibrosis triggered by two potent mediators, transforming growth factor–β (TGF-β) and bleomycin, in human and mouse tissues in vitro, ex vivo, and in vivo. We identified one peptide, E4, with potent antifibrotic activity. E4 prevented TGF-β–induced dermal fibrosis in vivo in a mouse model, ex vivo in human skin, and in bleomycin-induced dermal and pulmonary fibrosis in vivo, demonstrating that E4 exerts potent antifibrotic effects. In addition, E4 significantly reduced existing fibrosis in these preclinical models. E4 amelioration of fibrosis was accompanied by reduced cell apoptosis and lower levels of lysyl oxidase, an enzyme that cross-links collagen, and Egr-1 (early growth response gene–1), a transcription factor that mediates the effects of several fibrotic triggers. Our findings identify E4 as a peptide with potent antifibrotic activity and a possible therapeutic agent for organ fibrosis.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A Peptide Derived from Endostatin Ameliorates Organ Fibrosis

et al. 2012

View full text Add to dashboard Cite

show abstract

“…Endostar, a novel modified human recombinant endostatin with an additional nine amino acids purified from Escherichia coli , was approved for the treatment of non–small cell lung cancer in combination with other chemotherapy drugs in China in 2005 [37]. Elevated levels of endostatin are observed in the BALF and serum of IPF patients, especially those with severe respiratory dysfunction, compared to patients without these clinical manifestations [38,39]. A previous study [40] showed that recombinant endostatin inhibited dermal fibrosis in an ex vivo human skin model, and a peptide derived from endostatin prevented dermal and lung fibrosis induced by BLM in a mouse model.…”

Section: Discussionmentioning

confidence: 99%

Endostatin, an angiogenesis inhibitor, ameliorates bleomycin-induced pulmonary fibrosis in rats

et al. 2013

View full text Add to dashboard Cite

BackgroundRecent evidence has demonstrated the role of angiogenesis in the pathogenesis of pulmonary fibrosis. Endostatin, a proteolytic fragment of collagen XVIII, is a potent inhibitor of angiogenesis. The aim of our study was to assess whether endostatin has beneficial effects on bleomycin (BLM)-induced pulmonary fibrosis in rats.MethodsThe rats were randomly divided into five experimental groups: (A) saline only, (B) BLM only, (C) BLM plus early endostatin treatment, (D) BLM plus late endostatin treatment, and (F) BLM plus whole-course endostatin treatment. We investigated the microvascular density (MVD), inflammatory response and alveolar epithelial cell apoptosis in rat lungs in each group at different phases of disease development.ResultsEarly endostatin administration attenuated fibrotic changes in BLM-induced pulmonary fibrosis in rats. Endostatin treatment decreased MVD by inhibiting the expression of VEGF/VEGFR-2 (Flk-1) and the activation of extracellular signal-regulated protein kinase 1/2 (ERK1/2). Endostatin treatment also decreased the number of inflammatory cells infiltrating the bronchoalveolar lavage fluid during the early inflammatory phase of BLM-induced pulmonary fibrosis. In addition, the levels of tumour necrosis factor-α (TNF-α) and transforming growth factor β1 (TGF-β1) were reduced by endostatin treatment. Furthermore, endostatin decreased alveolar type II cell apoptosis and had an epithelium-protective effect. These might be the mechanism underlying the preventive effect of endostatin on pulmonary fibrosis.ConclusionsOur findings suggest that endostatin treatment inhibits the increased MVD, inflammation and alveolar epithelial cell apoptosis, consequently ameliorating BLM-induced pulmonary fibrosis in rats.

show abstract

“…John et al (1999) purified different circulating endostatin forms from human blood ultrafiltrate (hemofiltrate). Changes in the level of the circulating endostatin have been observed both under physiological and pathological conditions (Gu et al 2004;Seko et al 2004;Sumi et al 2005) and may lead under certain Fig. 10 CLSM of the simultaneous detection of (a) endostatin and (b) a-smooth muscle actin within aortae of mice housed for 3 weeks at hypoxia.…”

Section: Discussionmentioning

confidence: 99%

Hypoxia-induced increase of endostatin in murine aorta and lung

Paddenberg

Faulhammer

Goldenberg

et al. 2006

Histochem Cell Biol

View full text Add to dashboard Cite

In the lung, hypoxia induces pulmonary hypertension caused by vasoconstriction and vascular remodeling. Additionally, hypoxia is an inducer of angiogenesis, which is assumed to counteract pulmonary hypertension. We asked whether the anti-angiogenic factor endostatin--a cleavage product of collagen XVIII--participates in the vascular alterations induced by hypoxia. By employing Western blotting of tissue extracts of murine brain, liver and heart an endostatin fragment of 22 kDa was detectable, whereas in lung and aorta additional bands of 24 and 26 kDa were found. The amount of these larger fragments was increased in tissues obtained from mice housed for 4 days or 3 weeks at hypobaric hypoxia. By immunohistochemistry endostatin was detected in association with elastic fibers and in close neighborhood to smooth muscle cells of intrapulmonary vessels and the aorta. In the lung, the activity of matrix metalloproteinases (MMP) known to generate endostatin by cleavage of collagen XVIII was increased (MMP-2) and decreased (proMMP-9), respectively, by hypoxia. Elevated amounts of endostatin within the aortic wall of mice exposed to hypobaric hypoxia may stabilize the vascular wall by inhibition of microvascular sprouting. The surprising finding of increased endostatin in the lung presumably contributes to the development of pulmonary hypertension by reduction of angiogenesis.

show abstract

Increased serum levels of endostatin in patients with idiopathic pulmonary fibrosis

Cited by 25 publications

References 18 publications

A Peptide Derived from Endostatin Ameliorates Organ Fibrosis

A Peptide Derived from Endostatin Ameliorates Organ Fibrosis

Endostatin, an angiogenesis inhibitor, ameliorates bleomycin-induced pulmonary fibrosis in rats

Hypoxia-induced increase of endostatin in murine aorta and lung

Contact Info

Product

Resources

About