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Modulation of AT-1R/MAPK cascade by an olmesartan treatment attenuates diabetic nephropathy in streptozotocin-induced diabetic mice.
Mol Cell Endocrinol. 2012 Jan 02; 348(1):104-11.MC

Abstract

There is increasing evidence that angiotensin (Ang)-II plays an unprecedented role in diabetic complications. It could also be an important therapeutic target for ameliorating various diseases, especially diabetic nephropathy (DN). We therefore studied the beneficial effects of olmesartan, an Ang-II type 1 receptor (AT-1R) blocker in streptozotocin (150 mg/kg, BW)-induced diabetic kidney disease in mice. The diabetic kidney mice displayed upregulated protein expression levels of AT-1R, AT-2R, ERK-1/2, p-p38 MAPK, p-MAPKAPK-2, ET-1, p-JNK, p-c-Jun, TGF-β1, and gp91-phox, and all of these effects were expectedly downregulated by an olmesartan treatment. Also, immunohistochemical analysis, and Azan-Mallory and HE staining were performed to examine the expression of collagen-III and fibronectin, renal fibrosis, and hypertrophy, respectively. Furthermore, olmesartan treatment significantly abrogated the downregulation of ACE-2 and Ang-(1-7) mas R protein expression in diabetic kidney mice. Considering all these findings together, the AT-1R/MAPK pathway might be a potential therapeutic target in diabetes kidney disease, and olmesartan treatment could have beneficial effects on DN by modulating the AT-1R/MAPK pathway.

Authors+Show Affiliations

Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata City 956-8603, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21827824

Citation

Lakshmanan, Arun Prasath, et al. "Modulation of AT-1R/MAPK Cascade By an Olmesartan Treatment Attenuates Diabetic Nephropathy in Streptozotocin-induced Diabetic Mice." Molecular and Cellular Endocrinology, vol. 348, no. 1, 2012, pp. 104-11.
Lakshmanan AP, Thandavarayan RA, Watanabe K, et al. Modulation of AT-1R/MAPK cascade by an olmesartan treatment attenuates diabetic nephropathy in streptozotocin-induced diabetic mice. Mol Cell Endocrinol. 2012;348(1):104-11.
Lakshmanan, A. P., Thandavarayan, R. A., Watanabe, K., Sari, F. R., Meilei, H., Giridharan, V. V., Sukumaran, V., Soetikno, V., Arumugam, S., Suzuki, K., & Kodama, M. (2012). Modulation of AT-1R/MAPK cascade by an olmesartan treatment attenuates diabetic nephropathy in streptozotocin-induced diabetic mice. Molecular and Cellular Endocrinology, 348(1), 104-11. https://doi.org/10.1016/j.mce.2011.07.041
Lakshmanan AP, et al. Modulation of AT-1R/MAPK Cascade By an Olmesartan Treatment Attenuates Diabetic Nephropathy in Streptozotocin-induced Diabetic Mice. Mol Cell Endocrinol. 2012 Jan 2;348(1):104-11. PubMed PMID: 21827824.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Modulation of AT-1R/MAPK cascade by an olmesartan treatment attenuates diabetic nephropathy in streptozotocin-induced diabetic mice. AU - Lakshmanan,Arun Prasath, AU - Thandavarayan,Rajarajan A, AU - Watanabe,Kenichi, AU - Sari,Flori R, AU - Meilei,Harima, AU - Giridharan,Vijayasree V, AU - Sukumaran,Vijayakumar, AU - Soetikno,Vivian, AU - Arumugam,Somasundaram, AU - Suzuki,Kenji, AU - Kodama,Makoto, Y1 - 2011/07/30/ PY - 2011/04/22/received PY - 2011/07/20/revised PY - 2011/07/22/accepted PY - 2011/8/11/entrez PY - 2011/8/11/pubmed PY - 2012/3/6/medline SP - 104 EP - 11 JF - Molecular and cellular endocrinology JO - Mol Cell Endocrinol VL - 348 IS - 1 N2 - There is increasing evidence that angiotensin (Ang)-II plays an unprecedented role in diabetic complications. It could also be an important therapeutic target for ameliorating various diseases, especially diabetic nephropathy (DN). We therefore studied the beneficial effects of olmesartan, an Ang-II type 1 receptor (AT-1R) blocker in streptozotocin (150 mg/kg, BW)-induced diabetic kidney disease in mice. The diabetic kidney mice displayed upregulated protein expression levels of AT-1R, AT-2R, ERK-1/2, p-p38 MAPK, p-MAPKAPK-2, ET-1, p-JNK, p-c-Jun, TGF-β1, and gp91-phox, and all of these effects were expectedly downregulated by an olmesartan treatment. Also, immunohistochemical analysis, and Azan-Mallory and HE staining were performed to examine the expression of collagen-III and fibronectin, renal fibrosis, and hypertrophy, respectively. Furthermore, olmesartan treatment significantly abrogated the downregulation of ACE-2 and Ang-(1-7) mas R protein expression in diabetic kidney mice. Considering all these findings together, the AT-1R/MAPK pathway might be a potential therapeutic target in diabetes kidney disease, and olmesartan treatment could have beneficial effects on DN by modulating the AT-1R/MAPK pathway. SN - 1872-8057 UR - https://www.unboundmedicine.com/medline/citation/21827824/Modulation_of_AT_1R/MAPK_cascade_by_an_olmesartan_treatment_attenuates_diabetic_nephropathy_in_streptozotocin_induced_diabetic_mice_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0303-7207(11)00454-0 DB - PRIME DP - Unbound Medicine ER -