{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T13:39:09Z","timestamp":1778938749341,"version":"3.51.4"},"reference-count":29,"publisher":"American Physiological Society","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Renal Physiology"],"published-print":{"date-parts":[[2009,5]]},"abstract":"<jats:p>It has been reported that mechanical strain activates extracellular signal-regulated protein kinases (ERK) without the involvement of angiotensin II (Ang II) in cardiomyocytes. We examined the effects of mechanical strain on ERK phosphorylation levels in the absence of Ang II using rat mesangial cells. The ratio of phosphorylated ERK (p-ERK) to total ERK expression was increased by cyclic mechanical strain in a time- and elongation strength-dependent manner. With olmesartan [Ang II type 1 receptor (AT1R) antagonist] pretreatment, p-ERK plateau levels decreased in a dose-dependent manner (EC<jats:sub>50<\/jats:sub>= 1.3 \u00d7 10<jats:sup>\u22128<\/jats:sup>M, maximal inhibition 50.6 \u00b1 11.0% at 10<jats:sup>\u22125<\/jats:sup>M); a similar effect was observed with RNA interference against Ang II type 1A receptor (AT<jats:sub>1A<\/jats:sub>R) and Tempol, a superoxide dismutase mimetic. In addition to the inhibition of p-ERK levels, olmesartan blocked the increase in cell surface and phosphorylated p47<jats:sup>phox<\/jats:sup>induced by mechanical strain and also lowered the mRNA expression levels of NADPH oxidase subunits. These results demonstrate that mechanical strain stimulates AT1R to phosphorylate ERK in mesangial cells in the absence of Ang II. This mechanotransduction mechanism is involved in the oxidative stress caused by NADPH oxidase and is blocked by olmesartan. The inverse agonistic activity of this AT1R blocker may be useful for the prevention of mesangial proliferation and renal damage caused by mechanical strain\/oxidative stress regardless of circulating or tissue Ang II levels.<\/jats:p>","DOI":"10.1152\/ajprenal.00580.2007","type":"journal-article","created":{"date-parts":[[2009,3,5]],"date-time":"2009-03-05T02:10:05Z","timestamp":1236219005000},"page":"F1052-F1060","source":"Crossref","is-referenced-by-count":32,"title":["Angiotensin II type 1 receptor blocker attenuates the activation of ERK and NADPH oxidase by mechanical strain in mesangial cells in the absence of angiotensin II"],"prefix":"10.1152","volume":"296","author":[{"given":"Junichi","family":"Yatabe","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hironobu","family":"Sanada","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Midori Sasaki","family":"Yatabe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shigeatsu","family":"Hashimoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Minoru","family":"Yoneda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robin A.","family":"Felder","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pedro A.","family":"Jose","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tsuyoshi","family":"Watanabe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","reference":[{"key":"R1","unstructured":"Ardaillou R, Chansel D, Chatziantoniou C, Dussaule JC.Mesangial AT1 receptors: expression, signaling, and regulation.J Am Soc Nephrol10,Suppl11: S40\u2013S46, 1999."},{"key":"R2","doi-asserted-by":"publisher","DOI":"10.1007\/s001090100210"},{"key":"R3","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardiores.2004.08.007"},{"key":"R4","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-6147(03)00233-5"},{"key":"R5","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00476.2002"},{"key":"R6","doi-asserted-by":"publisher","DOI":"10.1042\/cs0910155"},{"key":"R7","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20031614"},{"key":"R8","doi-asserted-by":"crossref","unstructured":"Gruden G, Thomas S, Burt D, Zhou W, Chusney G, Gnudi L, Viberti G.Interaction of angiotensin II and mechanical stretch on vascular endothelial growth factor production by human mesangial cells.J Am Soc Nephrol10: 730\u2013737, 1999.","DOI":"10.1681\/ASN.V104730"},{"key":"R9","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.1998.00908.x"},{"key":"R10","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2004.12.087"},{"key":"R11","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2005050522"},{"key":"R12","doi-asserted-by":"publisher","DOI":"10.1097\/01.ASN.0000092145.90389.65"},{"key":"R13","unstructured":"Lee MA, Bohm M, Paul M, Ganten D.Tissue renin-angiotensin systems. 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