Human liver-type fatty acid-binding protein protects against tubulointerstitial injury in aldosterone-induced renal injury

Am J Physiol Renal Physiol. 2015 Jan 15;308(2):F114-21. doi: 10.1152/ajprenal.00469.2014. Epub 2014 Oct 22.


To demonstrate the renoprotective function of human liver-type fatty acid-binding protein (hL-FABP) expressed in proximal tubules in aldosterone (Aldo)-induced renal injury, hL-FABP chromosomal transgenic (Tg) and wild-type (WT) mice received systemic Aldo infusions (Tg-Aldo and WT-Aldo, respectively) were given 1% NaCl water for 28 days. In this model, elevation of systolic blood pressure, monocyte chemoattractant protein-1 expression, macrophage infiltration in the interstitium, tubulointerstitial damage, and depositions of type I and III collagens were observed. Elevation of systolic blood pressure did not differ in WT-Aldo vs. Tg-Aldo animals, however, renal injury was suppressed in Tg-Aldo compared with WT-Aldo mice. Dihydroethidium fluorescence was used to evaluate reactive oxidative stress, which was suppressed in Tg-Aldo compared with WT-Aldo mice. Gene expression of angiotensinogen in the kidney was upregulated, and excretion of urinary angiotensinogen was increased in WT-Aldo mice. This exacerbation was suppressed in Tg-Aldo mice. Expression of hL-FABP was upregulated in proximal tubules of Tg-Aldo mice. Urinary excretion of hL-FABP was significantly greater in Tg-Aldo than in Tg-control mice. In conclusion, hL-FABP ameliorated the tubulointerstitial damage in Aldo-induced renal injury via reducing oxidative stress and suppressing activation of the intrarenal renin-angiotensin system.

Keywords: L-FABP; activation of the intrarenal renin-angiotensin system; aldosterone; oxidative stress; tubulointerstitial damage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aldosterone / administration & dosage
  • Aldosterone / metabolism*
  • Angiotensinogen / metabolism
  • Animals
  • Blood Pressure / drug effects
  • Chemokine CCL2 / metabolism
  • Collagen Type I / metabolism
  • Collagen Type III / metabolism
  • Disease Models, Animal
  • Fatty Acid-Binding Proteins / metabolism*
  • Kidney / metabolism
  • Kidney / pathology
  • Macrophages / pathology
  • Male
  • Mice
  • Mice, Transgenic
  • Oxidative Stress
  • Renal Insufficiency / metabolism*
  • Renal Insufficiency / pathology
  • Renal Insufficiency / physiopathology
  • Renin-Angiotensin System*


  • Ccl2 protein, mouse
  • Chemokine CCL2
  • Collagen Type I
  • Collagen Type III
  • FABP1 protein, human
  • Fatty Acid-Binding Proteins
  • Angiotensinogen
  • Aldosterone