Search Results

You are looking at 1 - 5 of 5 items for

  • Author: Yoshihiro Ogawa x
Clear All Modify Search
Restricted access

Kenji Ogawa, Kenichiro Ono, Masamichi Kurohmaru and Yoshihiro Hayashi

Ogawa K, Ono K, Kurohmaru M, Hayashi Y. Effect of streptozotocin injection on expression of immunoreactive follistatin and βA and βB subunits of inhibin/activin in rat pancreatic islets. Eur J Endocrinol 1995;132:363–9. ISSN 0804–4643

The effect of streptozotocin (STZ) on expression of immunoreactive follistatin and β-subunits of inhibin/activin in pancreatic islets was studied by immunohistochemistry. To localize immunoreactive follistatin in pancreatic islets, two different anti-follistatin sera were used. Anti-follistatin(300–315) serum detects only long-form follistatin, while anti-follistatin(123–134) serum detects both long- and C-terminal truncated short-form follistatin in sodium dodecyl sulfate polyacrylamide gel electrophoresis and immunoblotting. Although an intense reaction with anti-follistatin(123–134) was found in pancreatic B cells, a reaction with anti-follistatin(300–315) was not present in any type of cells. This result suggests that only short-form follistatin is expressed in pancreatic islets. It was confirmed that immunoreaction with anti-βA(1–10)-Tyr serum was found in pancreatic B cells. The anti-βB(1–10)-Tyr reaction was intense in A cells but weak in B cells. These findings suggest that the expression pattern of each β-subunit differs in each type of islet cells. At 2 weeks after STZ injection (65 mg/kg), insulin immunoreaction still remained in B cells, although most pancreatic B cells were destroyed. In contrast, immunoreactions of follistatin and β-subunits in B cells disappeared 24 h after STZ treatment. These results indicate that STZ affects the production of follistatin or β-subunits of inhibin/activin in pancreatic B cells rather than insulin secretion.

Kenji Ogawa, Department of Veterinary Anatomy, Faculty of Agriculture, The University of Tokyo, Bunkyo-ku, Tokyo 113, Japan

Free access

Masanori Murakami, Takanobu Yoshimoto, Kazuhiko Nakabayashi, Kyoichiro Tsuchiya, Isao Minami, Ryotaro Bouchi, Hajime Izumiyama, Yasuhisa Fujii, Kosei Abe, Chiharu Tayama, Koshi Hashimoto, Takayoshi Suganami, Ken-ichiro Hata, Kazunori Kihara and Yoshihiro Ogawa

Objective

The pathophysiology of aldosterone-producing adenomas (APA) has been investigated intensively through genetic and genomic approaches. However, the role of epigenetics in APA is not fully understood. In the present study, we explored the relationship between gene expression and DNA methylation status in APA.

Methods

We conducted an integrated analysis of transcriptome and methylome data of paired APA-adjacent adrenal gland (AAG) samples from the same patient. The adrenal specimens were obtained from seven Japanese patients with APA who underwent adrenalectomy. Gene expression and genome-wide CpG methylation profiles were obtained from RNA and DNA samples that were extracted from those seven paired tissues.

Results

Methylome analysis showed global CpG hypomethylation in APA relative to AAG. The integration of gene expression and methylation status showed that 34 genes were up-regulated with CpG hypomethylation in APA. Of these, three genes (CYP11B2, MC2R, and HPX) may be related to aldosterone production, and five genes (PRRX1, RAB38, FAP, GCNT2, and ASB4) are potentially involved in tumorigenesis.

Conclusion

The present study is the first methylome analysis to compare APA with AAG in the same patients. Our integrated analysis of transcriptome and methylome revealed DNA hypomethylation in APA and identified several up-regulated genes with DNA hypomethylation that may be involved in aldosterone production and tumorigenesis.

Restricted access

Yujiro Nakano, Takanobu Yoshimoto, Ryo Watanabe, Masanori Murakami, Tatsuya Fukuda, Kazutaka Saito, Yasuhisa Fujii, Takumi Akashi, Toshihiro Tanaka, Tetsuya Yamada, Mitsuhide Naruse and Yoshihiro Ogawa

Objective

The pathophysiology of aldosterone-producing adenomas (APAs) has been intensively investigated using genetic and epigenetic approaches. However, the role of miRNAs in APA is not fully understood. The present study profiled miRNAs in APAs as an exploratory approach to elucidate their pathophysiological roles in APAs.

Design

Tissues of APAs and other adrenocortical adenomas were obtained from patients who underwent adrenalectomy.

Methods

Candidate miRNAs differentially detected from samples were examined by whole miRNA sequencing. The expression of candidate miRNAs in APA tissues were further validated by real-time quantitative polymerase chain reaction (qPCR). Further, differential miRNA expression between APAs with and without KCNJ5 somatic mutations was examined. Prediction of miRNA target genes was performed by bioinformatics analysis. For specific miRNAs, correlation analysis between the levels of their target genes and CYP11B2 was analyzed in APA tissues.

Results

Our study determined differential expression of six miRNAs in APA or APA with KCNJ5 mutations. We further demonstrated that miR299 levels were negatively correlated with mRNA levels of CACNB2, which encodes the beta-subunit of the L-type calcium channel. Additionally, we found significant correlations among miR299, CACNB2, and CYP11B2 levels in APA tissues.

Conclusions

Our study suggests the possible pathophysiological involvement of specific miRNAs in calcium signaling and aldosterone hypersecretion in APAs. Further studies, including in vitro analyses, are required to clarify these findings.

Restricted access

Hiroki Kobayashi, Yoshihiro Nakamura, Masanori Abe, Isao Kurihara, Hiroshi Itoh, Takamasa Ichijo, Yoshiyu Takeda, Takashi Yoneda, Takuyuki Katabami, Mika Tsuiki, Norio Wada, Yoshihiro Ogawa, Ryuichi Sakamoto, Junji Kawashima, Masakatsu Sone, Nobuya Inagaki, Takanobu Yoshimoto, Tetsuya Yamada, Ryuji Okamoto, Yuichi Matsuda, Megumi Fujita, Minemori Watanabe, Kouichi Tamura, Akiyo Tanabe, Mitsuhide Naruse and JPAS/JRAS Study Group

Objectives

We investigated the clinical significance of ACTH stimulation during adrenal venous sampling (AVS) by surgical outcome of primary aldosteronism (PA).

Design

Multicenter retrospective study by Japan PA study.

Method

We allocated 314 patients with both basal and ACTH-stimulated AVS data who underwent adrenalectomy to three groups: basal lateralization index (LI) ≥2 with ACTH-stimulated LI ≥4 on the ipsilateral side (Unilateral (U) to U group, n = 245); basal LI <2 with ACTH-stimulated LI ≥4 (Bilateral (B) to U group, n = 15); and basal LI ≥2 with ACTH-stimulated LI <4 (U to B group, n = 54). We compared surgical outcomes among the groups using the Primary Aldosteronism Surgical Outcome (PASO) criteria.

Results

Compared with U to U group, U to B group had poor clinical and biochemical outcomes and low rates of adrenal adenoma as pathological findings (P = 0.044, 0.006, and 0.048, respectively), although there were no significant differences between U to U and B to U groups. All patients in U to B group with clinical and biochemical benefits, however, had adrenal adenoma as pathological findings and could be well differentiated from those with poor surgical outcomes via basal LI (>8.3), but not ACTH-stimulated LI. These results were similar even when we defined each group based on a cut-off value of 4 for basal LI.

Conclusions

Although PA patients in U to B group had worse surgical outcomes than did those in U to U group, basal LI could discriminate among patients with better surgical outcomes in U to B group.

Restricted access

Akiyuki Kawashima, Masakatsu Sone, Nobuya Inagaki, Yoshiyu Takeda, Hiroshi Itoh, Isao Kurihara, Hironobu Umakoshi, Takamasa Ichijo, Takuyuki Katabami, Norio Wada, Yoshihiro Ogawa, Junji Kawashima, Megumi Fujita, Shozo Miyauchi, Shintaro Okamura, Tomikazu Fukuoka, Toshihiko Yanase, Shoichiro Izawa, Yuichiro Yoshikawa, Shigeatsu Hashimoto, Masanobu Yamada, Tatsuya Kai, Tomoko Suzuki, Mitsuhide Naruse and the JPAS and JRAS groups

Objective

Several clinical studies have reported that renal impairments are sometimes observed in patients with primary aldosteronism (PA). We analyzed the prevalence of renal impairments in PA patients and identified parameters that increase the risk for them.

Design

This is a retrospective cross-sectional study. We assessed the PA database established by the multicenter Japan PA study (JPAS). Data were also collected from patients with essential hypertension (EHT).

Methods

We compared the prevalences of proteinuria and lowered estimated glomerular filtration rate (eGFR) between patients with PA and age, sex, blood pressure and duration of hypertension-matched patients with EHT. We also performed logistic regression analysis to identify parameters that increase the risk for these renal impairments.

Results

Among 2366 PA patients, the prevalences of proteinuria and lowered eGFR were 10.3 and 11.6%, respectively. The prevalence of proteinuria was significantly higher in PA patients than matched-EHT patients (16.8 vs 4.4%), whereas there was no significant difference in the prevalence of lowered eGFR (17.2 vs 15.0%). The logistic regression analysis also showed that the plasma aldosterone concentration (PAC) significantly increases the risk of proteinuria and lowered eGFR, independent of other known risk factors.

Conclusion

Plasma aldosterone levels are closely associated with renal impairment in patients with PA. This is contrast to our earlier finding that the PAC was not itself linearly associated with cardiovascular events such as stroke or ischemic heart disease. The mechanism underlying the kidney damage in patients with PA may differ from that affecting the cardiovascular system.