- 著者
- Kan SAITO Nobukazu ISHIZAKA Toru AIZAWA Masataka SATA Naoyuki ISO-O Eisei NOIRI Minoru OHNO Ryozo NAGAI
- 出版者
- The Japanese Society of Hypertension
- 雑誌
- Hypertension Research (ISSN:09169636)
- 巻号頁・発行日
- vol.27, no.8, pp.599-607, 2004 (Released:2004-10-19)
- 参考文献数
- 30
- 被引用文献数
- 18 27
We have previously shown that abnormal iron metabolism might be one underlying mechanism of the renal damage observed in the angiotensin II-infused rat. Transforming growth factor-β1 (TGF-β1) is known to play a crucial role in the development of renal damage induced by activation of the renin-angiotensin-aldosterone system. The purpose of the present study was to examine the effects of an iron chelator and a free radical scavenger on the angiotensin II-induced upregulation of TGF-β1 in the kidney. Rats were given angiotensin II (0.7 mg/kg/day) via osmotic minipumps for 7 days. The expressions of the mRNAs of TGF-β1 and collagen types I and IV were significantly increased in response to angiotensin II treatment. Histologic analysis showed that TGF-β1 expression was upregulated mainly in tubular epithelial cells, and occasionally in glomerular and perivascular cells, some of which were identified as monocytes and/or macrophages. Although tubular cells that overexpressed TGF-β1 did not contain iron particles, angiotensin II-induced TGF-β1 upregulation was suppressed by the iron chelator and the free radical scavenger. The free radical scavenger also suppressed angiotensin II-induced upregulation of heme oxygenase-1, an oxidative-stress sensitive gene. By contrast, administration of iron dextran to rats induced upregulation of TGF-β1 mRNA. Collectively, these data suggest that the renal iron overload and presumed subsequent increase in oxidative stress play a role in angiotensin II-induced upregulation of the mRNAs of TGF-β1 and collagen types I and IV in the kidney. (Hypertens Res 2004; 27: 599-607)
- 著者
- Takahiro Miyakoshi Rie Oka Yasuto Nakasone Yuka Sato Keishi Yamauchi Rie Hashikura Masayuki Takayama Yudai Hirayama Kazuko Hirabayashi Hideo Koike Toru Aizawa
- 出版者
- (社)日本内分泌学会
- 雑誌
- Endocrine Journal (ISSN:09188959)
- 巻号頁・発行日
- vol.63, no.9, pp.857-865, 2016 (Released:2016-09-30)
- 参考文献数
- 25
- 被引用文献数
- 11
To develop diabetes risk score (RS) based on the current definition of diabetes, we retrospectively analyzed consecutive 4,159 health examinees who were non-diabetic at baseline. Diabetes, diagnosed by fasting plasma glucose (FPG) ≥7.0 mmol/L, 2hPG ≥11.1 mmol/L and/or HbA1c ≥6.5% (48 mmol/mol), developed in 279 of them during the mean period of 4.9 years. A full RS (RSFull), a RS without 2hPG (RS-2hPG) and a non-invasive RS (RSNI) were created on the basis of multivariate Cox proportional model by weighted grading based on hazard ratio in half the persons assigned. The RSs were verified in the remaining half of the participants. Positive family history (FH), male sex, smoking and higher age, systolic blood pressure (SBP), FPG, 2hPG and HbA1c were independent predictors for RSFull. For RS-2hPG, 7 independent predictors, exclusive of 2hPG and smoking but inclusive of elevated triglycerides (TG) comparing to RSFull, were selected. FH, male sex, and higher age, SBP and HbA1c were independent predictors in RSNI. In the validation cohort, C-statistic (95%CI) of RSFull, RS-2hPG and RSNI were 0.80 (0.76-0.84), 0.75 (0.70-0.78) and 0.68 (0.63-0.72), respectively, which were significantly different from each other (P <0.01). Absolute percentage difference between predicted probability and observed diabetes were 1.9%, 0.7% and 0.9%, by the three scores, respectively, and not significantly different from each other. In conclusion, diabetes defined by the current criteria was predicted by the new diabetes risk scores with reasonable accuracy. Nonetheless, RSFull with a postchallenge glucose value performed superior to RS-2hPG and RSNI.