Klotho expression abnormalities induces kidney injury and chronic kidney disease, however, the underlying mechanism remains unclear. Here, Klotho^+/- mice and wild-type mice were treated with low-dose bovine serum albumin (BSA). Pathological examination demonstrated that the area of glomerular collagen deposition and fibrosis in BSA-Kl^-/+ mice was significantly larger than that in BSA-WT mice. The serum levels of superoxide dismutase, malondialdehyde, creatinine, and urea in BSA-Kl^-/+ mice were significantly increased. Sequencing of gut microbiota 16S rRNA v3-v4 region indicated that BSA-Kl^-/+ mice showed a significantly higher relative abundance of the genera Dubosiella, Akkermansia, Alloprevotella, and Lachnospiraceae and a significantly lower relative abundance of the genera Allobaculum and Muribaculaceae than BSA-WT mice. KEGG analysis revealed that the metabolic pathways of signal transduction, xenobiotic biodegradation and metabolism, and lipid metabolism increased significantly in BSA-Kl^-/+ mice. Flow cytometry showed that the proportion of CD68⁺/CD11b⁺ cells in the peripheral blood was significantly higher in BSA-KL^-/+ mice than that in BSA-WT mice. qPCR and western blot suggested that Klotho and Nrf2 expression in MΦ1 cells of BSA-KL^-/+ mice was significantly decreased. Thus, the findings suggest during the immune activation and chronic inflammation induced by the gut microbiota imbalance in Klotho-deficient mice treated to BSA, disrupted expression of proteins in the Nrf2/NF-κB signaling pathway in monocyte-derived macrophage M1 cells leads to the aggravation of inflammation and kidney injury.

中文翻译：

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牛血清白蛋白通过肠道微生物群免疫轴加重杂合 Klotho 缺陷小鼠的巨噬细胞 M1 活化和肾损伤

Klotho 表达异常会导致肾损伤和慢性肾病，但其潜在机制仍不清楚。在这里，Klotho ^+/-小鼠和野生型小鼠接受了低剂量牛血清白蛋白 (BSA) 的治疗。病理检查表明，BSA-K1 ^-/+小鼠肾小球胶原沉积和纤维化面积明显大于BSA-WT小鼠。^{BSA-K1 -/+}小鼠中超氧化物歧化酶、丙二醛、肌酐和尿素的血清水平显着增加。肠道微生物群 16S rRNA v3-v4 区域的测序表明 BSA-K1 ^{-/+小鼠显示出显着更高的}Dubosiella、Akkermansia属的相对丰度、Alloprevotella和Lachnospiraceae以及Allobaculum和Muribaculaceae属的相对丰度显着低于BSA-WT 小鼠。^{KEGG分析显示，在BSA-K1 -/+}小鼠中，信号转导、外源生物降解和代谢以及脂质代谢的代谢途径显着增加。流式细胞仪显示， BSA-KL ^-/+小鼠外周血中CD68 ⁺ /CD11b ⁺细胞的比例显着高于BSA-WT小鼠。qPCR 和蛋白质印迹表明 Klotho 和 Nrf2 在 BSA-KL 的 MΦ1 细胞中表达^-/+小鼠明显减少。因此，研究结果表明，在接受 BSA 治疗的 Klotho 缺陷小鼠的肠道微生物群失衡诱导的免疫激活和慢性炎症期间，单核细胞衍生的巨噬细胞 M1 细胞中 Nrf2/NF-κB 信号通路中蛋白质的表达中断导致加重炎症和肾损伤。