Eplerenone reduces lymphangiogenesis in the contralateral kidneys of UUO rats

TL;DR

This study shows that eplerenone can reduce lymphangiogenesis and fibrosis in the healthy kidney of rats with one blocked ureter.

Contribution

The study reveals a novel mechanism involving mineralocorticoid receptors in contralateral kidney injury and fibrosis.

Findings

Mineralocorticoid receptor activation promotes lymphangiogenesis in the contralateral kidney after injury.

Eplerenone blocks this process and reduces fibrotic injury in the unaffected kidney.

Lymphatic endothelial cells contribute to fibrosis by secreting myofibroblast markers.

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.

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