Altered expression of angiogenic factors in the VEGF-Ets-1 cascades in inflammatory bowel disease

Konno, Shiho; Iizuka, Masahiro; Yukawa, Michihiro; Sasaki, Katsuhiko; Satô, Akiko; Horie, Yasuo; Nanjo, Hiroshi; Fukushima, Tsuneo; Watanabe, Sumio

doi:10.1007/s00535-004-1423-9

Cited by 33 publications

(24 citation statements)

References 41 publications

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“…In previous studies, an increased expression of VEGF protein and VEGF mRNA in UC patients had already been observed in comparison with those found in healthy controls [25,[34][35][36][37][38]. Our results were consistent with those found in previous studies using active UC patient blood samples [25,34,35].…”

Section: Discussionsupporting

confidence: 95%

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Corticosteroids Modulate Angiogenic Soluble Factors in Ulcerative Colitis Patients

et al. 2010

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VEGF, Ang1, and Ang2 levels showed statistically significant differences between UC patients and healthy controls. Although determination of PlGF serum levels before corticosteroid treatment might be helpful to anticipate the response by UC patients, no angiogenic pattern that could accurately predict "a priori" this response to corticosteroid treatment was observed. Corticosteroids altered temporarily circulating levels of VEGF, angiopoietins and Tie2. No correlation was found between systemic levels of angiogenic factors and the clinical activity of UC.

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Section: Discussionsupporting

confidence: 95%

“…Regarding the VEGFR1 tissue expression in these patients, there were diverse results in previous studies. Similarly, other authors also found an increased expression of both VEGFR1 protein and mRNA in UC inflamed mucosa [37].…”

Section: Discussionmentioning

confidence: 93%

Corticosteroids Modulate Angiogenic Soluble Factors in Ulcerative Colitis Patients

et al. 2010

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“…The increase in VEGF expression is mostly evident in the crypt region of the pouch mucosa, whereas in the ileal nonpouch mucosa obtained from the same patients and in the control ileal mucosa from patients with IBS, the immunostaining for VEGF is almost totally confined to the superficial epithelium. An increase in VEGF expression has previously been reported in the mucosa of patients with inflammatory bowel disease 23,24 and particularly in patients with ulcerative colitis. 25 To our knowledge this is the first report that shows upregulation of VEGF expression in IPAA.…”

Section: Discussionmentioning

confidence: 94%

Vascular Endothelial Growth Factor and Cyclooxygenase-2 are Overexpressed in Ileal Pouch-Anal Anastomosis

Romano¹,

Cuomo²,

Tuccillo³

et al. 2007

Diseases of the Colon &Amp; Rectum

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“…49 Studies have indicated reduced expression of Ets1 in PBMCs of patients with systemic lupus erythematosus and patients with inflammatory bowel disease. 50,51 Ets1 has also been reported to regulate the suppressive activity of MDSCs in tolerance induction to CD8 1 T cells. 52 Glucocorticoids modulate cell fate by altering gene expression via the glucocorticoid receptor (GR).…”

Section: Discussionmentioning

confidence: 99%

High-dose dexamethasone corrects impaired myeloid-derived suppressor cell function via Ets1 in immune thrombocytopenia

Hou

Feng

Xu³

et al. 2016

Blood

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Key Points• The impaired suppressive function of myeloid-derived suppressor cells plays a role in the pathogenesis of immune thrombocytopenia.• The effect of dexamethasone in correcting dysfunction of myeloid-derived suppressor cells suggests a new therapeutic mechanism of high-dose dexamethasone in patients with immune thrombocytopenia.Myeloid-derived suppressor cells (MDSCs) are heterogeneous immature cells and natural inhibitors of adaptive immunity. In this study, the MDSC population was evaluated in adult patients with primary immune thrombocytopenia (ITP), where cell-mediated immune mechanisms are involved in platelet destruction. Our data demonstrated that both the numbers and suppressive functions of MDSCs were impaired in the peripheral blood and spleens of patients with ITP compared with healthy control patients. High-dose dexamethasone (HD-DXM) treatment rescued MDSC numbers in patients with ITP. And DXM modulation promoted the suppressive function of MDSCs induced in vitro. Moreover, the expression of interleukin 10 and transforming growth factor b was significantly upregulated in DXM-modulated MDSCs compared with the unmodulated cultures. DXMmodulated MDSCs inhibited autologous CD4 1 T-cell proliferation and significantly attenuated cytotoxic T lymphocyte-mediated platelet lysis, further indicating enhanced control over T-cell responses. Elevated expression of the transcription factor Ets1 was identified in DXM-modulated MDSCs. Transfection of Ets-1 small interfering RNA efficiently blocked regulatory effects of MDSCs, which almost offset the augmentation of MDSC function by DXM. Meanwhile, splenocytes from CD61 knockout mice immunized with CD61 1 platelets were transferred into severe combined immunodeficient (SCID) mouse recipients (C57/B6 background) to induce a murine model of severe ITP. We passively transferred the DXM-modulated MDSCs induced from bone marrow of wild-type C57/B6 mice into the SCID mouse recipients, which significantly increased platelet counts in vivo compared with those receiving splenocyte engraftment alone. These findings suggested that impaired MDSCs are involved in the pathogenesis of ITP, and that HD-DXM corrected MDSC functions via a mechanism underlying glucocorticoid action and Ets1.

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Altered expression of angiogenic factors in the VEGF-Ets-1 cascades in inflammatory bowel disease

Abstract: Angiogenic factors in the VEGF-Ets-1 cascades were upregulated in UC, but they were relatively downregulated in CD. These alterations might be involved in the pathogenesis of both diseases.

Cited by 33 publications

References 41 publications

Corticosteroids Modulate Angiogenic Soluble Factors in Ulcerative Colitis Patients

Corticosteroids Modulate Angiogenic Soluble Factors in Ulcerative Colitis Patients

Vascular Endothelial Growth Factor and Cyclooxygenase-2 are Overexpressed in Ileal Pouch-Anal Anastomosis

High-dose dexamethasone corrects impaired myeloid-derived suppressor cell function via Ets1 in immune thrombocytopenia

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