Supplementary Material for: Effect of youthful blood environment and its key factor SCF on renal interstitial fibrosis in elderly mice

Introduction: Youthful blood environment was shown to decelerate the aging process of 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. Methods: 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. Results: 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 wildtype UUO mice, the expressions of pNF-κB and fibrosis-related proteins, and the kidney function were all significantly decreased in Wps/Wps UUO mice. Conclusion: Youthful blood environment downregulated the expressions of SCF/c-Kit in elderly UUO mice, and ameliorated UUO-induced kidney fibrosis and function loss.

研究背景：在年轻-老年异种共生动物模型中，年轻血液环境已被证实可延缓肾脏衰老进程，并减轻老年肾纤维化；此外，本团队还鉴定出一种与该过程密切相关的干细胞因子（stem cell factor, SCF）。本研究旨在探究年轻血液环境对老年肾间质纤维化的影响，以及SCF在其中发挥的作用。
研究方法：本研究繁育了干细胞因子受体c-Kit基因功能缺失型Wps/Wps小鼠，并构建了同时接受单侧输尿管梗阻（unilateral ureteral obstructive, UUO）手术与异种共生手术的复合小鼠模型。将异种共生小鼠分为同龄异种共生组（年轻-年轻组，Y-IP与老年-老年组，O-IP）以及异龄异种共生组（年轻-老年组，HP）。在同龄异种共生组中，对一对共生小鼠中的一只实施UUO手术（分别记为Y-IPuuo组与O-IPuuo组）；在异龄异种共生组中，则对老年共生小鼠实施UUO手术（记为O-HPuuo组）。为探究SCF/c-Kit在肾间质纤维化中的作用，本研究对野生型（wildtype, WT）小鼠与Wps/Wps小鼠实施UUO手术。
研究结果：UUO术后14天，O-HPuuo组的肾间质纤维化面积、肾功能以及SCF/c-Kit、磷酸化核因子κB（pNF-κB）与纤维化相关蛋白的表达水平，均显著低于Ouuo组与O-IPuuo组。与野生型UUO小鼠相比，Wps/Wps UUO小鼠的pNF-κB与纤维化相关蛋白表达水平以及肾功能均显著降低。
研究结论：年轻血液环境可下调老年UUO小鼠体内SCF/c-Kit的表达水平，并改善UUO诱导的肾脏纤维化与肾功能损伤。