Interactions of transforming growth factor-β and angiotensin II in renal fibrosis

被引:404
|
作者
Border, WA [1 ]
Noble, NA [1 ]
机构
[1] Univ Utah, Hlth Sci Ctr, Dept Med, Div Nephrol & Hypertens, Salt Lake City, UT 84132 USA
关键词
transforming growth factor-beta; angiotensin II; kidney; fibrosis;
D O I
10.1161/01.HYP.31.1.181
中图分类号
R6 [外科学];
学科分类号
1002 ; 100210 ;
摘要
Overproduction of transforming growth factor-beta clearly underlies tissue fibrosis in numerous experimental and human diseases. Transforming growth factor-beta's powerful fibrogenic action results from simultaneous stimulation of matrix protein synthesis, inhibition of matrix degradation, and enhanced integrin expression that facilitates matrix assembly. In animals, overexpression of transforming growth factor-beta 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-beta has been demonstrated in glomerulonephritis, diabetic nephropathy, and hypertensive glomerular injury. A possible explanation for the kidney's particular susceptibility to fibrosis may be the recent discovery of biologically complex interactions between the renin-angiotensin system and transforming growth factor-beta. Alterations in glomerular hemodynamics can activate both the renin-angiotensin system and transforming growth factor-beta. Components of the renin-angotensin system act to further stimulate production of transforming growth factor-beta and plasminogen activator inhibitor leading to rapid matrix accumulation. In volume depletion, transforming growth factor-beta 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-beta 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-beta production. This suggests that transforming growth factor-beta, 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.
引用
收藏
页码:181 / 188
页数:8
相关论文
共 50 条
  • [1] Local angiotensin II and transforming growth factor-β1 in renal fibrosis of rats
    Sun, Y
    Zhang, JK
    Zhang, JQ
    Ramires, FJA
    [J]. HYPERTENSION, 2000, 35 (05) : 1078 - 1084
  • [2] Transforming Growth Factor-β and Angiotensin in Fibrosis and Burn Injuries
    Gabriel, Vincent Ashley
    [J]. JOURNAL OF BURN CARE & RESEARCH, 2009, 30 (03): : 471 - 481
  • [3] Deleting Transforming Growth Factor-β type II receptor increases renal fibrosis
    Gewin, L. S.
    Zent, R.
    [J]. JOURNAL OF INVESTIGATIVE MEDICINE, 2008, 56 (01) : 480 - 480
  • [4] Transforming growth factor-β and fibrosis
    Franck Verrecchia
    Alain Mauviel
    [J]. World Journal of Gastroenterology, 2007, (22) : 3056 - 3062
  • [5] Transforming growth factor-β and fibrosis
    Verrecchia, Franck
    Mauviel, Alain
    [J]. WORLD JOURNAL OF GASTROENTEROLOGY, 2007, 13 (22) : 3056 - 3062
  • [6] Hypertension, transforming growth factor-β, angiotensin II and kidney disease
    Bobik, A
    [J]. JOURNAL OF HYPERTENSION, 2004, 22 (07) : 1265 - 1267
  • [7] Transforming growth factor-β in tissue fibrosis
    Frangogiannis, Nikolaos G.
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 2020, 217 (03):
  • [8] Angiotensin II, transforming growth factor-β1 and repair in the infarcted heart
    Sun, YO
    Zhang, JQ
    Zhang, JK
    Ramires, FJA
    [J]. JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, 1998, 30 (08) : 1559 - 1569
  • [9] Blocking of angiotensin II is more than blocking of transforming growth factor-β
    Daniel, Christoph
    [J]. KIDNEY INTERNATIONAL, 2008, 74 (05) : 551 - 553
  • [10] Contributions of angiotensin II and tumor necrosis factor-α to the development of renal fibrosis
    Guo, GJ
    Morrissey, J
    McCracken, R
    Tolley, T
    Liapis, H
    Klahr, S
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY, 2001, 280 (05) : F777 - F785