Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 7008558, Japan.
Department of Human Resource Development of Dialysis Therapy for Kidney Disease, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 7008558, Japan.
Int J Mol Sci. 2020 Jun 26;21(12):4545. doi: 10.3390/ijms21124545.
Acute kidney injury (AKI) has been increasingly recognized as a risk factor for transition to chronic kidney disease. Recent evidence suggests that endothelial damage in peritubular capillaries can accelerate the progression of renal injury. Vasohibin-2 (VASH2) is a novel proangiogenic factor that promotes tumor angiogenesis. However, the pathophysiological roles of VASH2 in kidney diseases remain unknown. In the present study, we examined the effects of VASH2 deficiency on the progression of ischemia-reperfusion (I/R) injury-induced AKI. I/R injury was induced by bilaterally clamping renal pedicles for 25 min in male wild-type (WT) and homozygous knockout mice. Twenty-four hours later, I/R injury-induced renal dysfunction and tubular damage were more severe in VASH2-deficient mice than in WT mice, with more prominent neutrophil infiltration and peritubular capillary loss. After induction of I/R injury, VASH2 expression was markedly increased in injured renal tubules. These results suggest that VASH2 expression in renal tubular epithelial cells might be essential for alleviating I/R injury-induced AKI, probably through protecting peritubular capillaries and preventing inflammatory infiltration.
急性肾损伤 (AKI) 已被越来越多地认为是向慢性肾脏病进展的危险因素。最近的证据表明，肾小管周围毛细血管的内皮损伤可加速肾损伤的进展。血管生成素-2（VASH2）是一种新型的促血管生成因子，可促进肿瘤血管生成。然而，VASH2 在肾脏疾病中的病理生理作用尚不清楚。在本研究中，我们研究了 VASH2 缺乏对缺血再灌注（I/R）损伤诱导的 AKI 进展的影响。通过双侧夹闭肾蒂 25 分钟在雄性野生型（WT）和纯合敲除小鼠中诱导 I/R 损伤。24 小时后，VASH2 缺陷型小鼠的 I/R 损伤诱导的肾功能障碍和肾小管损伤比 WT 小鼠更严重，中性粒细胞浸润和肾小管周围毛细血管丢失更明显。在诱导 I/R 损伤后，损伤的肾小管中 VASH2 的表达明显增加。这些结果表明，肾小管上皮细胞中 VASH2 的表达可能对于缓解 I/R 损伤诱导的 AKI 至关重要，可能是通过保护肾小管周围毛细血管和防止炎症浸润。
