Graduate School, Hebei University of Chinese Medicine, Shijiazhuang, China.
Hebei Key Laboratory of Integrative Medicine on Liver-Kidney Patterns, Hebei University of Chinese Medicine, Shijiazhuang, China.
Sci Rep. 2024 May 1;14(1):9976. doi: 10.1038/s41598-024-60636-z.
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.
在急性损伤后，肾脏常发生炎症和纤维化，导致慢性肾脏病和随后的肾衰竭。最近的研究表明，淋巴管生成可驱动损伤肾脏的炎症和纤维化。然而，这种发病机制是否以及如何影响对侧肾脏在很大程度上仍然未知。在我们的研究中，我们揭示了对侧肾脏对损伤做出反应的一种机制。我们发现，单侧输尿管梗阻后对侧肾脏中醛固酮受体的激活和血管内皮生长因子 C 的增加可促进淋巴管生成。此外，淋巴内皮细胞中醛固酮受体的激活导致肌成纤维细胞标志物的分泌，从而导致肾脏纤维化。我们观察到，通过给予醛固酮受体阻滞剂螺内酯可减轻这一过程，从而防止单侧输尿管梗阻大鼠对侧肾脏的纤维化损伤的发展。这些发现为肾脏损伤的复杂机制提供了有价值的见解，可能对开发治疗策略以减轻肾脏病中肾脏纤维化具有重要意义。
