FullText URL K0005592_other1.pdf
Author Hinamoto, Norikazu| Maeshima, Yohei| Yamasaki, Hiroko| Nasu, Tatsuyo| Saito, Daisuke| Watatani, Hiroyuki| Ujike, Haruyo| Tanabe, Katsuyuki| Masuda, Kana| Arata, Yuka| Sugiyama, Hitoshi| Sato, Yasufumi| Makino, Hirofumi|
Note 学位審査副論文
Published Date 2014-09-25
Publication Title Plos One
Volume volume9
Issue issue9
Publisher Public Library of Science
Start Page e107934
ISSN 1932-6203
Content Type Journal Article
language 英語
OAI-PMH Set 岡山大学
Copyright Holders https://creativecommons.org/licenses/by-nc-nd/4.0/
File Version publisher
PubMed ID 25255225
DOI 10.1371/journal.pone.0107934
Web of Sience KeyUT 000344862300045
Related Url isVersionOf https://doi.org/10.1371/journal.pone.0107934 isPartOf http://ousar.lib.okayama-u.ac.jp/55517
JaLCDOI 10.18926/AMO/55434
FullText URL 71_5_369.pdf
Author Arata, Yuka| Tanabe, Katsuyuki| Hinamoto, Norikazu| Yamasaki, Hiroko| Sugiyama, Hitoshi| Maeshima, Yohei| Kanomata, Naoki| Sato, Yasufumi| Wada, Jun|
Abstract Several angiogenesis-related factors are known to play important roles in the pathogenesis of kidney disease. Vasohibin-2 (VASH-2) was recently reported as a novel proangiogenic factor. Although VASH-2 was demonstrated to accelerate tumor angiogenesis, its roles in non-tumor processes including renal disease have not been well elucidated yet. Here, we performed a retrospective study including an immunohistochemical analysis of human kidney biopsy specimens from 82 Japanese patients with a variety of kidney diseases, and we evaluated the correlations between the immunoreactivity of VASH-2 and the patients’ clinicopathological parameters. VASH-2 immunoreactivity was detected in varying degrees in renal tubules as well as in peritubular capillaries and vasa recta. The cortical and medullary tubule VASH-2+ scores were correlated with the presence of hypertension, and the medullary tubule VASH-2+ score was significantly correlated with the blood glucose (p=0.029, r=0.35) and hemoglobin A1c levels (p=0.0066, r=0.39). Moreover, decreased VASH-2+ scores in the vasa recta were associated with reduced renal function (p=0.0003). These results suggest that VASH-2 could play an important role in the pathogenesis of renal diseases, and that VASH-2 is closely associated with hypertension and impaired glucose tolerance.
Keywords vasohibin-2 kidney disease vasa recta medullary tubules
Amo Type Original Article
Published Date 2017-10
Publication Title Acta Medica Okayama
Volume volume71
Issue issue5
Publisher Okayama University Medical School
Start Page 369
End Page 380
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language 英語
Copyright Holders CopyrightⒸ 2017 by Okayama University Medical School
File Version publisher
Refereed True
PubMed ID 29042694
JaLCDOI 10.18926/AMO/53117
FullText URL 69_1_1.pdf
Author Watatani, Hiroyuki| Yamasaki, Hiroko| Maeshima, Yohei| Nasu, Tatsuyo| Hinamoto, Norikazu| Ujike, Haruyo| Sugiyama, Hitoshi| Sakai, Yoshiki| Tanabe, Katsuyuki| Makino, Hirofumi|
Abstract Diabetic nephropathy is the most common pathological disorder predisposing patients to end-stage renal disease. Considering the increasing prevalence of type 2 diabetes mellitus worldwide, novel therapeutic approaches are urgently needed. ONO-1301 is a novel sustained-release prostacyclin analog that inhibits thromboxane A2 synthase. Here we examined the therapeutic effects of the intermittent administration of slow-release ONO-1301 (SR-ONO) on diabetic nephropathy in obese type 2 diabetes mice, as well as its direct effects on mesangial cells. The subcutaneous injection of SR-ONO (3mg/kg) every 3 wks did not affect the obesity or hyperglycemia in the db/db obese mice used as a model of type 2 diabetes, but it significantly ameliorated their albuminuria, glomerular hypertrophy, glomerular accumulation of type IV collagen, and monocyte/macrophage infiltration, and also the increase of TGF-β1, α-smooth muscle actin (α-SMA) and MCP-1 compared to vehicle treatment. In cultured mouse mesangial cells, ONO-1301 concentration-dependently suppressed the increases in TGF-β, type IV collagen, α-SMA, MCP-1 and fibronectin induced by high ambient glucose, at least partly through prostacyclin (PGI2) receptor-mediated signaling. Taken together, these results suggest the potential therapeutic efficacy of the intermittent administration of SR-ONO against type 2 diabetic nephropathy, possibly through protective effects on mesangial cells.
Keywords prostacyclin ONO-1301 diabetic nephropathy TGF-β1 diabetes mellitus
Amo Type Original Article
Published Date 2015-02
Publication Title Acta Medica Okayama
Volume volume69
Issue issue1
Publisher Okayama University Medical School
Start Page 1
End Page 15
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language 英語
Copyright Holders CopyrightⒸ 2015 by Okayama University Medical School
File Version publisher
Refereed True
PubMed ID 25703166
Web of Science KeyUT 000349740300001
Related Url http://ousar.lib.okayama-u.ac.jp/metadata/53128
JaLCDOI 10.18926/AMO/52788
FullText URL 68_4_219.pdf
Author Hinamoto, Norikazu| Maeshima, Yohei| Saito, Daisuke| Yamasaki, Hiroko| Tanabe, Katsuyuki| Nasu, Tatsuyo| Watatani, Hiroyuki| Ujike, Haruyo| Kinomura, Masaru| Sugiyama, Hitoshi| Sonoda, Hikaru| Kanomata, Naoki| Sato, Yasufumi| Makino, Hirofumi|
Abstract Experimental studies have demonstrated the involvement of angiogenesis-related factors in the progression of chronic kidney disease (CKD). There have so far been no reports investigating the distribution and clinical roles of Vasohibin-1 (VASH-1), a negative feedback regulator of angiogenesis, in CKD. We recruited 54 Japanese CKD patients and 6 patients who had normal renal tissues excised due to localized renal cell carcinoma. We evaluated the correlations between the renal expression level of VASH-1 and the clinical/histological parameters. VASH-1 was observed in renal endothelial/mesangial cells, crescentic lesions and interstitial inflammatory cells. Significant positive correlations were observed between 1) crescent formation and the number of VASH-1+ cells in the glomerulus (r=0.48, p=0.001) or cortex (r=0.64, p<0.0001), 2) interstitial cell infiltration and the number of VASH-1+ cells in the cortex (r=0.34, p=0.02), 3) the glomerular VEGFR-2+ area and the number of VASH-1+ cells in the glomerulus (r=0.44, p=0.01) or medulla (r=0.63, p=0.01). These results suggest that the renal levels of VASH-1 may be affected by local inflammation, crescentic lesions and VEGFR-2.
Keywords chronic kidney disease inflammation Vasohibin-1 VEGF-A VEGFR-2
Amo Type Original Article
Published Date 2014-08
Publication Title Acta Medica Okayama
Volume volume68
Issue issue4
Publisher Okayama University Medical School
Start Page 219
End Page 233
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language 英語
Copyright Holders CopyrightⒸ 2014 by Okayama University Medical School
File Version publisher
Refereed True
PubMed ID 25145408
Web of Sience KeyUT 000340687500004
Related Url http://ousar.lib.okayama-u.ac.jp/metadata/52824
JaLCDOI 10.18926/AMO/31820
FullText URL fulltext.pdf
Author Miyake, Kohei| Nishida, Keiichiro| Kadota, Yasutaka| Yamasaki, Hiroko| Nasu, Tatsuyo| Saitou, Daisuke| Tanabe, Katsuyuki| Sonoda, Hikaru| Sato, Yasufumi| Maeshima, Yohei| Makino, Hirofumi|
Abstract <p>Angiogenesis is an essential event in the development of synovial inflammation in rheumatoid arthritis (RA). The aim of the current study was to investigate the expression of vasohibin-1, a novel endothelium-derived vascular endothelial growth factor (VEGF)-inducible angiogenesis inhibitor, in the RA synovium, and to test the effect of inflammatory cytokines on the expression of vasohibin-1 by RA synovial fibroblasts (RASFs). Synovial tissue samples were obtained at surgery from patients with osteoarthritis (OA) and RA, and subjected to immunohistochemistry to investigate the expression and distribution of vasohibin-1 relevant to the degree of synovial inflammation. In an in vitro analysis, RASFs were used to examine the expression of vasohibin-1 and VEGF mRNA by real-time PCR after stimulation with VEGF or inflammatory cytokines under normoxic or hypoxic conditions. The immunohistochemical results showed that vasohibin-1 was expressed in synovial lining cells, endothelial cells, and synovial fibroblasts. In synovial tissue, there was a significant correlation between the expression of vasohibin-1 and histological inflammation score (p0.002, r0.842). In vitro, stimulation with VEGF induced the expression of vasohibin-1 mRNA in RASFs under normoxic conditions, and stimulation with cytokines induced vasohibin-1 mRNA expression under a hypoxic condition. These results suggest that vasohibin-1 was expressed in RA synovial tissue and might be regulated by inflammatory cytokines.</p>
Keywords angiogenesis vasohibin-1 rheumatoid arthritis synovial membrane VEGF
Amo Type Original Article
Published Date 2009-12
Publication Title Acta Medica Okayama
Volume volume63
Issue issue6
Publisher Okayama University Medical School
Start Page 349
End Page 358
ISSN 0386-300X
NCID AA00508441
Content Type Journal Article
language 英語
File Version publisher
Refereed True
PubMed ID 20035291
Web of Sience KeyUT 000273145900006