The presence of xanthine dehydrogenase is crucial for the maturation of the rat kidneys

黄嘌呤脱氢酶 脱氢酶 黄嘌呤 内科学 内分泌学 化学 医学 生物 生物化学 黄嘌呤氧化酶
作者
Lashodya V. Dissanayake,Olha Kravtsova,Melissa Lowe,Marice K. McCrorey,Justin P. Van Beusecum,Oleg Palygin,Alexander Staruschenko
出处
期刊:Clinical Science [Portland Press]
卷期号:138 (5): 269-288 被引量:1
标识
DOI:10.1042/cs20231144
摘要

Abstract The development of the kidney involves essential cellular processes, such as cell proliferation and differentiation, which are led by interactions between multiple signaling pathways. Xanthine dehydrogenase (XDH) catalyzes the reaction producing uric acid in the purine catabolism, which plays a multifaceted role in cellular metabolism. Our previous study revealed that the genetic ablation of the Xdh gene in rats leads to smaller kidneys, kidney damage, decline of renal functions, and failure to thrive. Rats, unlike humans, continue their kidney development postnatally. Therefore, we explored whether XDH plays a critical role in kidney development using SSXdh-/- rats during postnatal development phase. XDH expression was significantly increased from postnatal day 5 to 15 in wild-type but not homozygote rat kidneys. The transcriptomic profile of renal tissue revealed several dysregulated pathways due to the lack of Xdh expression with the remodeling in inflammasome, purinergic signaling, and redox homeostasis. Further analysis suggested that lack of Xdh affects kidney development, likely via dysregulation of epidermal growth factor and its downstream STAT3 signaling. The present study showed that Xdh is essential for kidney maturation. Our data, alongside the previous research, suggests that loss of Xdh function leads to developmental issues, rendering them vulnerable to kidney diseases in adulthood.
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