Eplerenone reduces lymphangiogenesis in the contralateral kidneys of UUO rats

Sci Rep. 2024 May 1;14(1):9976. doi: 10.1038/s41598-024-60636-z.

Abstract

Inflammation and fibrosis often occur in the kidney after acute injury, resulting in chronic kidney disease and consequent renal failure. Recent studies have indicated that lymphangiogenesis can drive renal inflammation and fibrosis in injured kidneys. However, whether and how this pathogenesis affects the contralateral kidney remain largely unknown. In our study, we uncovered a mechanism by which the contralateral kidney responded to injury. We found that the activation of mineralocorticoid receptors and the increase in vascular endothelial growth factor C in the contralateral kidney after unilateral ureteral obstruction could promote lymphangiogenesis. Furthermore, mineralocorticoid receptor activation in lymphatic endothelial cells resulted in the secretion of myofibroblast markers, thereby contributing to renal fibrosis. We observed that this process could be attenuated by administering the mineralocorticoid receptor blocker eplerenone, which, prevented the development of fibrotic injury in the contralateral kidneys of rats with unilateral ureteral obstruction. These findings offer valuable insights into the intricate mechanisms underlying kidney injury and may have implications for the development of therapeutic strategies to mitigate renal fibrosis in the context of kidney disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism
  • Endothelial Cells / pathology
  • Eplerenone* / pharmacology
  • Fibrosis* / drug therapy
  • Kidney* / drug effects
  • Kidney* / metabolism
  • Kidney* / pathology
  • Lymphangiogenesis* / drug effects
  • Male
  • Mineralocorticoid Receptor Antagonists* / pharmacology
  • Myofibroblasts / drug effects
  • Myofibroblasts / metabolism
  • Myofibroblasts / pathology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Mineralocorticoid / metabolism
  • Spironolactone / analogs & derivatives
  • Spironolactone / pharmacology
  • Ureteral Obstruction* / complications
  • Ureteral Obstruction* / drug therapy
  • Ureteral Obstruction* / metabolism
  • Ureteral Obstruction* / pathology
  • Vascular Endothelial Growth Factor C / metabolism

Substances

  • Eplerenone
  • Mineralocorticoid Receptor Antagonists
  • Receptors, Mineralocorticoid
  • Spironolactone
  • Vascular Endothelial Growth Factor C