{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T10:43:44Z","timestamp":1793357024919,"version":"4.5.0"},"reference-count":62,"publisher":"American Physiological Society","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Renal Physiology"],"published-print":{"date-parts":[[2008,8]]},"abstract":"<jats:p>Activation of the renin-angiotensin system contributes to the progression of chronic kidney disease. Based on the known cellular effects of ANG II to promote inflammation, we posited that stimulation of lymphocyte responses by ANG II might contribute to the pathogenesis of hypertensive kidney injury. We therefore examined the effects of the immunosuppressive agent mycophenolate mofetil (MMF) on the course of hypertension and kidney disease induced by chronic infusion of ANG II in 129\/SvEv mice. Although it had no effect on the severity of hypertension or cardiac hypertrophy, treatment with MMF significantly reduced albuminuria and ameliorated kidney injury, decreasing glomerulosclerosis and reducing lymphocyte infiltration into the renal interstitium. Attenuation of renal pathology with MMF was associated with reduced expression of mRNAs for the proinflammatory cytokines interferon-\u03b3 and tumor necrosis factor-\u03b1 and the profibrotic cytokine transforming growth factor-\u03b2. As infiltration of the kidney by T lymphocytes was a prominent feature of ANG II-dependent renal injury, we carried out experiments examining the effects of ANG II on lymphocytes in vitro. We find that exposure of splenic lymphocytes to ANG II causes prominent rearrangements of the actin cytoskeleton. These actions require the activity of Rho kinase. Thus, ANG II exaggerates hypertensive kidney injury by stimulating lymphocyte responses. These proinflammatory actions of ANG II seem to have a proclivity for inducing kidney injury while having negligible actions in the pathogenesis of cardiac hypertrophy.<\/jats:p>","DOI":"10.1152\/ajprenal.00527.2007","type":"journal-article","created":{"date-parts":[[2008,5,21]],"date-time":"2008-05-21T20:54:26Z","timestamp":1211403266000},"page":"F515-F524","source":"Crossref","is-referenced-by-count":143,"title":["Stimulation of lymphocyte responses by angiotensin II promotes kidney injury in hypertension"],"prefix":"10.1152","volume":"295","author":[{"given":"Steven D.","family":"Crowley","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Campbell W.","family":"Frey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha K.","family":"Gould","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Griffiths","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phillip","family":"Ruiz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James L.","family":"Burchette","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David N.","family":"Howell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Makhanova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyung-Suk","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre-Louis","family":"Tharaux","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas M.","family":"Coffman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.18.1.165"},{"key":"R2","doi-asserted-by":"crossref","unstructured":"Amuchastegui SC\n                      , Azzollini N, Mister M, Pezzotta A, Perico N, Remuzzi G.\n                      Chronic allograft nephropathy in the rat is improved by angiotensin II receptor blockade but not by calcium channel antagonism.\n                      J Am Soc Nephrol\n                      9\n                      : 1948\u20131955, 1998.","DOI":"10.1681\/ASN.V9101948"},{"key":"R3","doi-asserted-by":"publisher","DOI":"10.1172\/JCI750"},{"key":"R4","unstructured":"Baudeau C\n                      , Delarue F, He CJ, Nguyen G, Adida C, Peraldi MN, Sraer JD, Rondeau E.\n                      Induction of MHC class II molecules HLA-DR,DP and -DQ and ICAM 1 in human podocytes by gamma-interferon.\n                      Exp Nephrol\n                      2\n                      : 306\u2013312, 1994."},{"key":"R5","unstructured":"Bertani T\n                      , Abbate M, Zoja C, Corna D, Perico N, Ghezzi P, Remuzzi G.\n                      Tumor necrosis factor induces glomerular damage in the rabbit.\n                      Am J Pathol\n                      134\n                      : 419\u2013430, 1989."},{"key":"R6","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.31.1.181"},{"key":"R7","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa011161"},{"key":"R8","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81380-X"},{"key":"R9","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9149(01)01538-7"},{"key":"R10","unstructured":"Casellas D\n                      , Benahmed S, Artuso A, Jover B.\n                      Candesartan and progression of preglomerular lesions in\n                      N\n                      G\n                      -nitro-\n                      l\n                      -arginine methyl ester hypertensive rats.\n                      J Am Soc Nephrol\n                      10\n                      ,\n                      Suppl\n                      11: S230\u2013S233, 1999."},{"key":"R11","doi-asserted-by":"publisher","DOI":"10.1159\/000164052"},{"key":"R12","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0605545103"},{"key":"R13","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-201X.2004.01331.x"},{"key":"R14","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(02)08089-3"},{"key":"R15","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000141573.44737.5A"},{"key":"R16","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.1998.00026.x"},{"key":"R17","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M103484200"},{"key":"R18","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.0000112225.27560.24"},{"key":"R19","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.37.1.170"},{"key":"R20","unstructured":"Gomez-Chiarri M\n                      , Ortiz A, Lerma JL, Lopez-Armada MJ, Mampaso F, Gonzalez E, Egido J.\n                      Involvement of tumor necrosis factor and platelet-activating factor in the pathogenesis of experimental nephrosis in rats.\n                      Lab Invest\n                      70\n                      : 449\u2013459, 1994."},{"key":"R21","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.0000049881.25304.73"},{"key":"R22","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.02231205"},{"key":"R23","doi-asserted-by":"publisher","DOI":"10.1038\/317361a0"},{"key":"R24","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20070657"},{"key":"R25","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfg299"},{"key":"R26","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.95.6.1532"},{"key":"R27","doi-asserted-by":"publisher","DOI":"10.1172\/JCI4189"},{"key":"R28","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfi303"},{"key":"R29","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.8.3521"},{"key":"R30","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2249.1999.00901.x"},{"key":"R31","doi-asserted-by":"publisher","DOI":"10.1172\/JCI117251"},{"key":"R32","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00423.2003"},{"key":"R33","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.072083799"},{"key":"R34","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.301.2.459"},{"key":"R35","doi-asserted-by":"publisher","DOI":"10.1038\/nm1275"},{"key":"R36","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa011303"},{"key":"R37","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.18.9.1408"},{"key":"R38","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2003.00058.x"},{"key":"R39","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2005.02.004"},{"key":"R40","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.0000228320.23697.29"},{"key":"R41","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.33.1.389"},{"key":"R42","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2005030297"},{"key":"R43","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.35.1.193"},{"key":"R44","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)64445-8"},{"key":"R45","doi-asserted-by":"publisher","DOI":"10.1172\/JCI7451"},{"key":"R46","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfg034"},{"key":"R47","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2001.00737.x"},{"key":"R48","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.1999.055003945.x"},{"key":"R49","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2000.00089.x"},{"key":"R50","doi-asserted-by":"publisher","DOI":"10.1016\/S0962-8924(99)01553-6"},{"key":"R51","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.0000075082.06183.4E"},{"key":"R52","doi-asserted-by":"crossref","unstructured":"Sharma R\n                      , Lovell HB, Wiegmann TB, Savin VJ.\n                      Vasoactive substances induce cytoskeletal changes in cultured rat glomerular epithelial cells.\n                      J Am Soc Nephrol\n                      3\n                      : 1131\u20131138, 1992.","DOI":"10.1681\/ASN.V351131"},{"key":"R53","doi-asserted-by":"crossref","unstructured":"Spurney RF\n                      , Ibrahim S, Butterly D, Klotman PE, Sanfilippo F, Coffman TM.\n                      Leukotrienes in renal transplant rejection in rats. Distinct roles for leukotriene B4 and peptidoleukotrienes in the pathogenesis of allograft injury.\n                      J Immunol\n                      152\n                      : 867\u2013876, 1994.","DOI":"10.4049\/jimmunol.152.2.867"},{"key":"R54","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1991.12"},{"key":"R55","doi-asserted-by":"publisher","DOI":"10.1016\/S1357-2725(02)00271-6"},{"key":"R56","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.171.1.96"},{"key":"R57","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00007.2005"},{"key":"R58","doi-asserted-by":"crossref","unstructured":"Van Bruggen MC\n                      , Walgreen B, Rijke TP, Berden JH.\n                      Attenuation of murine lupus nephritis by mycophenolate mofetil.\n                      J Am Soc Nephrol\n                      9\n                      : 1407\u20131415, 1998.","DOI":"10.1681\/ASN.V981407"},{"key":"R59","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000024416.33113.0A"},{"key":"R60","doi-asserted-by":"publisher","DOI":"10.1177\/43.3.7868861"},{"key":"R61","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119615"},{"key":"R62","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ki.5001625"}],"container-title":["American Journal of Physiology-Renal Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/ajprenal.00527.2007","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,18]],"date-time":"2023-05-18T09:12:51Z","timestamp":1684401171000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/ajprenal.00527.2007"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,8]]},"references-count":62,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2008,8]]}},"alternative-id":["10.1152\/ajprenal.00527.2007"],"URL":"https:\/\/doi.org\/10.1152\/ajprenal.00527.2007","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.1111111.567086","asserted-by":"object"}]},"ISSN":["1931-857X","1522-1466"],"issn-type":[{"value":"1931-857X","type":"print"},{"value":"1522-1466","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,8]]}}}