Increased Prorenin Expression in the Kidneys May Be Involved in the Abnormal Renal Function Caused by Prolonged Environmental Exposure to Microcystin-LR
Yuuka Hitsuda,
Yoshihito Koto,
Hideaki Kawahara,
Koichi Kurata,
Keisuke Yoshikiyo,
Kohji Nishimura,
Ayumi Hashiguchi,
Hideaki Maseda,
Kunihiro Okano,
Norio Sugiura,
Kazuya Shimizu,
Hidehisa Shimizu
Affiliations
Yuuka Hitsuda
Graduate School of Natural Science and Technology, Shimane University, 1060 Nishikawatsu-Cho, Matsue 690-8504, Japan
Yoshihito Koto
Graduate School of Natural Science and Technology, Shimane University, 1060 Nishikawatsu-Cho, Matsue 690-8504, Japan
Hideaki Kawahara
Graduate School of Life and Environmental Science, Shimane University, 1060 Nishikawatsu-Cho, Matsue 690-8504, Japan
Koichi Kurata
Graduate School of Life and Environmental Science, Shimane University, 1060 Nishikawatsu-Cho, Matsue 690-8504, Japan
Keisuke Yoshikiyo
Graduate School of Natural Science and Technology, Shimane University, 1060 Nishikawatsu-Cho, Matsue 690-8504, Japan
Kohji Nishimura
Graduate School of Natural Science and Technology, Shimane University, 1060 Nishikawatsu-Cho, Matsue 690-8504, Japan
Ayumi Hashiguchi
Faculty of Environmental, Life, Natural Science and Technology, Okayama University, 3-1-1, Tsushima-Naka, Kita-ku, Okayama-shi 700-8530, Japan
Hideaki Maseda
Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology, 1-8-31 Midorigaoka, Osaka 563-8577, Japan
Kunihiro Okano
Faculty of Bioresource Sciences, Akita Prefectural University, Akita 010-0195, Japan
Norio Sugiura
Faculty of Life and Environmental Sciences, University of Tsukuba, Ibaraki 305-8572, Japan
Kazuya Shimizu
Faculty of Life Sciences, Toyo University, Gunma 374-0193, Japan
Hidehisa Shimizu
Graduate School of Natural Science and Technology, Shimane University, 1060 Nishikawatsu-Cho, Matsue 690-8504, Japan
Toxic algae in eutrophic lakes produce cyanotoxic microcystins. Prior research on the effect of microcystin-LR in the kidney utilized intraperitoneal injections, which did not reflect natural exposure. Oral microcystin-LR research has focused on renal function and histopathology without examining the molecular mechanisms. The present study aimed to evaluate the mechanism of microcystin-LR in the kidneys via oral administration in WKAH/HkmSlc rats over 7 weeks, alongside stimulation of the proximal tubular cells. Although there were no differences in the concentrations of plasma albumin, blood urea nitrogen, and creatinine, which are parameters of renal function, between the control and microcystin-LR-administrated rats, prorenin expression was significantly increased in the renal cortex of the rats administered microcystin-LR and the microcystin-LR-treated proximal tubular cells. The expression levels of (pro)renin receptor (PRR), transforming growth factor-β1 (TGFβ1), and α-smooth muscle actin (α-SMA) in the renal cortex did not differ significantly between the control and microcystin-LR-administered rats. However, the expression levels of prorenin were significantly positively correlated with those of PRR, TGFβ1, and α-SMA in the renal cortex of rats administered microcystin-LR. Additionally, a significant positive correlation was observed between the expression levels of TGFβ1 and α-SMA. Collectively, increased prorenin expression caused by the long-term consumption of microcystin-LR may initiate a process that influences renal fibrosis and abnormal renal function by regulating the expression levels of PRR, TGFβ1, and α-SMA.
