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Carnitine/organic cation transporter 1 precipitates the progression of interstitial fibrosis through oxidative stress in diabetic nephropathy in mice.
Sci Rep. 2021 Apr 27; 11(1):9093.SR

Abstract

Carnitine/organic cation transporter 1 (OCTN1) is the only known uptake transporter for ergothioneine which is a food-derived strong antioxidant amino acid that is absorbed by OCTN1. We previously reported the roles of OCTN1/ergothioneine in the progression of kidney fibrosis in ischemic kidney disease. In this study, we evaluated the roles of OCTN1 in the progression of diabetic kidney disease. A diabetic kidney disease model was induced in octn1 knockout and wild-type mice by streptozotocin (STZ). Oxidative stress, represented by urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG), were higher in the octn1 knockout mice. Azan- and Sirius red-positive areas increased significantly in the octn1 knockout mice. Gene expression was evaluated by cluster analysis, and shown to be different in the octn1 knockout mice compared with the wild-type mice. In a pathway analysis, the pathway associated with the cytoskeleton and cell adhesion increased. In accordance with interstitial fibrosis in octn1 knockout mice, gene expression of moesin in the injured kidney, known as an associated protein of cytoskeleton and cell membranes, was doubled 28 weeks after STZ injection. In addition, the moesin protein was expressed in a part of α-SMA-positive renal tubular epithelial cells. These findings were confirmed by cultured murine proximal tubular epithelial cells: The expression of moesin was induced under oxidative stress with hydrogen peroxide. These data indicate that OCTN1 would play some roles in progression of interstitial fibrosis under oxidative stress via moesin expression in diabetic kidney disease.

Authors+Show Affiliations

Department of Nephrology and Laboratory Medicine, Faculty of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Japan.Department of Nephrology, Kanazawa Medical University School of Medicine, Uchinada, Ishikawa, Japan. furuichi@kanazawa-med.ac.jp.Department of Nephrology and Laboratory Medicine, Faculty of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Japan.Department of Nephrology and Laboratory Medicine, Faculty of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Japan.Department of Nephrology and Laboratory Medicine, Faculty of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Japan.Department of Nephrology and Laboratory Medicine, Faculty of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Japan.Department of Nephrology and Laboratory Medicine, Faculty of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Japan.Department of Nephrology and Laboratory Medicine, Faculty of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Japan.Department of Nephrology and Laboratory Medicine, Faculty of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Japan.Department of Nephrology and Laboratory Medicine, Faculty of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Japan.Faculty of Pharmacy, Institute of Medical, Pharmaceutical and Health Science, Kanazawa University, Kanazawa, Japan.Department of System Biology, Kanazawa University, Kanazawa, Japan.Faculty of Pharmacy, Institute of Medical, Pharmaceutical and Health Science, Kanazawa University, Kanazawa, Japan.Department of Nephrology and Laboratory Medicine, Faculty of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Japan.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

33907247

Citation

Makiishi, Shohei, et al. "Carnitine/organic Cation Transporter 1 Precipitates the Progression of Interstitial Fibrosis Through Oxidative Stress in Diabetic Nephropathy in Mice." Scientific Reports, vol. 11, no. 1, 2021, p. 9093.
Makiishi S, Furuichi K, Yamamura Y, et al. Carnitine/organic cation transporter 1 precipitates the progression of interstitial fibrosis through oxidative stress in diabetic nephropathy in mice. Sci Rep. 2021;11(1):9093.
Makiishi, S., Furuichi, K., Yamamura, Y., Sako, K., Shinozaki, Y., Toyama, T., Kitajima, S., Iwata, Y., Sakai, N., Shimizu, M., Hirose-Sugiura, T., Kaneko, S., Kato, Y., & Wada, T. (2021). Carnitine/organic cation transporter 1 precipitates the progression of interstitial fibrosis through oxidative stress in diabetic nephropathy in mice. Scientific Reports, 11(1), 9093. https://doi.org/10.1038/s41598-021-88724-4
Makiishi S, et al. Carnitine/organic Cation Transporter 1 Precipitates the Progression of Interstitial Fibrosis Through Oxidative Stress in Diabetic Nephropathy in Mice. Sci Rep. 2021 Apr 27;11(1):9093. PubMed PMID: 33907247.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Carnitine/organic cation transporter 1 precipitates the progression of interstitial fibrosis through oxidative stress in diabetic nephropathy in mice. AU - Makiishi,Shohei, AU - Furuichi,Kengo, AU - Yamamura,Yuta, AU - Sako,Keisuke, AU - Shinozaki,Yasuyuki, AU - Toyama,Tadashi, AU - Kitajima,Shinji, AU - Iwata,Yasunori, AU - Sakai,Norihiko, AU - Shimizu,Miho, AU - Hirose-Sugiura,Tomoko, AU - Kaneko,Shuichi, AU - Kato,Yukio, AU - Wada,Takashi, Y1 - 2021/04/27/ PY - 2020/12/06/received PY - 2021/04/07/accepted PY - 2021/4/28/entrez PY - 2021/4/29/pubmed PY - 2021/4/29/medline SP - 9093 EP - 9093 JF - Scientific reports JO - Sci Rep VL - 11 IS - 1 N2 - Carnitine/organic cation transporter 1 (OCTN1) is the only known uptake transporter for ergothioneine which is a food-derived strong antioxidant amino acid that is absorbed by OCTN1. We previously reported the roles of OCTN1/ergothioneine in the progression of kidney fibrosis in ischemic kidney disease. In this study, we evaluated the roles of OCTN1 in the progression of diabetic kidney disease. A diabetic kidney disease model was induced in octn1 knockout and wild-type mice by streptozotocin (STZ). Oxidative stress, represented by urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG), were higher in the octn1 knockout mice. Azan- and Sirius red-positive areas increased significantly in the octn1 knockout mice. Gene expression was evaluated by cluster analysis, and shown to be different in the octn1 knockout mice compared with the wild-type mice. In a pathway analysis, the pathway associated with the cytoskeleton and cell adhesion increased. In accordance with interstitial fibrosis in octn1 knockout mice, gene expression of moesin in the injured kidney, known as an associated protein of cytoskeleton and cell membranes, was doubled 28 weeks after STZ injection. In addition, the moesin protein was expressed in a part of α-SMA-positive renal tubular epithelial cells. These findings were confirmed by cultured murine proximal tubular epithelial cells: The expression of moesin was induced under oxidative stress with hydrogen peroxide. These data indicate that OCTN1 would play some roles in progression of interstitial fibrosis under oxidative stress via moesin expression in diabetic kidney disease. SN - 2045-2322 UR - https://www.unboundmedicine.com/medline/citation/33907247/Carnitine/organic_cation_transporter_1_precipitates_the_progression_of_interstitial_fibrosis_through_oxidative_stress_in_diabetic_nephropathy_in_mice_ L2 - https://doi.org/10.1038/s41598-021-88724-4 DB - PRIME DP - Unbound Medicine ER -
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