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In animals, overexpression of transforming growth factor-\u03b2 by intravenous injection, transient gene transfer, or transgene insertion has shown that the kidney is highly susceptible to rapid fibrosis. The same seems true in human disease, where excessive transforming growth factor-\u03b2 has been demonstrated in glomerulonephritis, diabetic nephropathy, and hypertensive glomerular injury. A possible explanation for the kidney\u2019s particular susceptibility to fibrosis may be the recent discovery of biologically complex interactions between the renin-angiotensin system and transforming growth factor-\u03b2. Alterations in glomerular hemodynamics can activate both the renin-angiotensin system and transforming growth factor-\u03b2. Components of the renin-angiotensin system act to further stimulate production of transforming growth factor-\u03b2 and plasminogen activator inhibitor leading to rapid matrix accumulation. In volume depletion, transforming growth factor-\u03b2 is released from juxtaglomerular cells and may act synergistically with angiotensin II to accentuate vasoconstriction and acute renal failure. Interaction of the renin-angiotensin system and transforming growth factor-\u03b2 has important clinical implications. The protective effect of inhibition of the renin-angiotensin system in experimental and human kidney diseases correlates closely with the suppression of transforming growth factor-\u03b2 production. This suggests that transforming growth factor-\u03b2, in addition to blood pressure, should be a therapeutic target. Higher doses or different combinations of drugs that block the renin-angiotensin system or entirely new drug strategies may be needed to achieve a greater antifibrotic effect.<\/jats:p>","DOI":"10.1161\/01.hyp.31.1.181","type":"journal-article","created":{"date-parts":[[2012,6,12]],"date-time":"2012-06-12T00:53:46Z","timestamp":1339462426000},"page":"181-188","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":349,"title":["Interactions of Transforming Growth Factor-\u03b2 and Angiotensin II in Renal Fibrosis"],"prefix":"10.1161","volume":"31","author":[{"given":"Wayne A.","family":"Border","sequence":"first","affiliation":[{"name":"From the Division of Nephrology and Hypertension, Department of Medicine, University of Utah Health Sciences Center, Salt Lake City, Utah."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy A.","family":"Noble","sequence":"additional","affiliation":[{"name":"From the Division of Nephrology and Hypertension, Department of Medicine, University of Utah Health Sciences Center, Salt Lake City, Utah."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119419"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.20.11035"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1997.184"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1994.52"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.V7102025"},{"key":"e_1_3_2_6_2","first-page":"555","volume":"16","year":"1996","unstructured":"Fogo A, Kon V. 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