Department of Nephrology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing, China.
Gerontology. 2023;69(5):628-640. doi: 10.1159/000529399. Epub 2023 Jan 31.
Youthful blood environment was shown to decelerate the aging process of the kidney and to attenuate senile renal fibrosis in a young-old parabiotic animal model; in addition, we identified a stem cell factor (SCF) that is closely linked with the process. This research was to investigate the effect of youthful blood environment on senile renal interstitial fibrosis and the role of SCF.
We bred SCF receptor c-Kit gene loss-of-function Wps/Wps mice and established a combination mice model that was subjected to unilateral ureteral obstructive (UUO) and parabiotic surgeries. Parabiotic mice were divided into isochronic parabiotic (young-young [Y-IP] and old-old [O-IP]) and heterochronic parabiotic (young-old [HP]) groups. UUO surgery was performed in one of the parabiotic pairs in the IP group (Y-IPuuo and O-IPuuo) and in the elderly mice in the HP group (O-HPuuo). In order to study the role of SCF/c-kit on renal interstitial fibrosis, UUO surgery was performed in wildtype (WT) and Wps/Wps mice.
Fourteen days after UUO surgery, the kidney interstitial fibrosis area, kidney function, and the expressions of SCF/c-Kit, pNF-κB, and fibrosis-related proteins in the O-HPuuo group were significantly lower than those in the Ouuo and O-IPuuo groups. Compared with WT UUO mice, the expressions of pNF-κB and fibrosis-related proteins and the kidney function were all significantly decreased in Wps/Wps UUO mice.
Youthful blood environment downregulated the expressions of SCF/c-Kit in elderly UUO mice and ameliorated UUO-induced kidney fibrosis and function loss.
年轻血液环境被证明可以延缓肾脏衰老过程，并减轻年轻-老年联体动物模型中的老年肾纤维化；此外，我们还发现了一种与该过程密切相关的干细胞因子 (SCF)。本研究旨在探讨年轻血液环境对老年肾间质纤维化的影响及其与 SCF 的关系。
我们培育了 SCF 受体 c-Kit 基因缺失功能的 Wps/Wps 小鼠，并建立了单侧输尿管梗阻 (UUO) 和联体手术的组合小鼠模型。联体小鼠分为同龄联体 (年轻-年轻 [Y-IP] 和老年-老年 [O-IP]) 和异龄联体 (年轻-老年 [HP]) 组。在 IP 组中的一个联体对 (Y-IPuuo 和 O-IPuuo) 中对 UUO 手术进行操作，在 HP 组中的老年小鼠中进行 (O-HPuuo)。为了研究 SCF/c-kit 对肾间质纤维化的作用，在野生型 (WT) 和 Wps/Wps 小鼠中进行了 UUO 手术。
UUO 手术后 14 天，O-HPuuo 组的肾脏间质纤维化面积、肾功能以及 SCF/c-Kit、pNF-κB 和纤维化相关蛋白的表达均明显低于 Ouuo 和 O-IPuuo 组。与 WT UUO 小鼠相比，Wps/Wps UUO 小鼠的 pNF-κB 和纤维化相关蛋白表达以及肾功能均明显降低。
年轻血液环境下调了老年 UUO 小鼠中 SCF/c-Kit 的表达，并改善了 UUO 诱导的肾脏纤维化和功能丧失。
