In patients with chronic kidney disease, the abnormal activation of inflammatory pathways is usually an important factor leading to renal fibrosis and further deterioration of renal function. Finding effective intervention targets of the inflammatory signaling pathway is an important way to treat chronic kidney disease. As a newly discovered lysosomal membrane protein, the correlation between SID1 transmembrane family member 2 (Sidt2) and the inflammatory signaling pathway has not been reported. The aim of this study was to investigate the effect of Sidt2 on inflammation by inhibiting the expression of the Sidt2 gene in a mouse mesangial cell line mediated by a lentiviral CRISPR/Cas9 vector. Hematoxylin and eosin staining and microscopy found that the mesangial cells lost their normal morphology after inhibiting the expression of Sidt2, showing that the cell body became smaller, the edge between the cells was unclear, and part of the nucleus was pyknotic and fragmented, appearing blue-black. The expressions of IKK β, p-IKK α/β, NF-κB p65, p-NF-κB p65, p-IκBα, IκBα, and TNF-α in the NF-κB pathway of the Sidt2^-/- group were higher than those of the Sidt2^+/+ group. p-Jak2 and IL6 increased in the Jak/Stat pathway, and p-ERK and p-P38 increased in the MAPK pathway. The expressions of IKK β, p-IKK α/β, NF-κB p65, p-NF-κB p65, p-IκBα, IκBα, and TNF-α in the NF-κB pathway of the Sidt2^+/++LPS group were significantly higher than those in the Sidt2^+/+ group. The expressions of IKK β, p-IKK α/β, NF-κB p65, p-NF-κB p65, p-IκBα, IκBα, and TNF-α in the Sidt2^-/-+LPS group were higher than those in the Sidt2^-/- group. The expressions of p-IKK α/β, NF-κB p65, p-NF-κB p65, p-IκBα, IκBα, and TNF-α in the Sidt2^-/-+LPS group were higher than those in the Sidt2^+/++LPS group. In the Jak/Stat pathway, the protein expressions of p-Jak2 and IL6 in the Sidt2^+/++LPS group were higher than those in the Sidt2^+/+ group. The expressions of p-Jak2 and IL6 in the Sidt2^-/-+LPS group were higher than those in the Sidt2^-/- group. The expressions of p-Jak2 and IL6 in the Sidt2^-/-+LPS group were higher than those in the Sidt2^+/++LPS group. The expressions of p-JNK, p-ERK, p-P38, and ERK in the MAPK pathway in the Sidt2^+/++LPS group were higher than those in the Sidt2^+/+ group. The expressions of p-JNK, p-ERK, p-P38, and ERK in the Sidt2^-/-+LPS group were higher than those in the Sidt2^-/- group. The expressions of p-JNK, p-ERK, p-P38, and ERK in the Sidt2^-/-+LPS group were higher than those in the Sidt2^+/++LPS group. These data suggested that deletion of the Sidt2 gene changed the three inflammatory signal pathways, eventually leading to the damage of glomerular mesangial cells in mice.

中文翻译：

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Sidt2对小鼠肾小球系膜细胞炎性途径的影响。

在患有慢性肾脏疾病的患者中，炎症通路的异常激活通常是导致肾纤维化和肾功能进一步恶化的重要因素。寻找炎症信号通路的有效干预目标是治疗慢性肾脏疾病的重要方法。作为一种新发现的溶酶体膜蛋白，尚未报道SID1跨膜家族成员2（Sidt2）与炎症信号通路之间的相关性。这项研究的目的是通过抑制Sidt2的表达来研究Sidt2对炎症的影响慢病毒CRISPR / Cas9载体介导的小鼠肾小球系膜细胞基因 苏木精和曙红染色及显微镜检查发现，系膜细胞在抑制Sidt2表达后丧失了正常形态，表明细胞体变小，细胞间边缘不清晰，部分细胞核结节并破碎，呈蓝色。 -黑色。IKK的表达β，对IKK α / β，NF- κ乙P65，对NF- κ乙P65，等电点κ乙α，我κ B α，和TNF- α在NF- κ的乙途径Sidt2 ^-/-组高于Sidt2 ^{+ / +}组。在Jak / Stat途径中，p-Jak2和IL6升高，而在MAPK途径中，p-ERK和p-P38升高。IKK的表达β，对IKK α / β，NF- κ乙P65，对NF- κ乙P65，等电点κ乙α，我κ B α，和TNF- α在NF- κ的乙途径Sidt2 ^{+ / +} + LPS组明显高于Sidt2 ^{+ / +}组。IKK的表达β，对IKK α /β，NF- κ乙P65，对NF- κ乙P65，等电点κ乙α，我κ乙α，和TNF- α中Sidt2 ^{- / -} + LPS组较在较高Sidt2 ^{- / -}组。对IKK的表达α / β，NF- κ乙P65，对NF- κ乙P65，等电点κ乙α，我κ B α，和TNF- α中Sidt2 ^{- / -} + LPS组均高于Sidt2中的那些^{+ / +}+ LPS组。在Jak / Stat途径中，Sidt2 ^{+ / +} + LPS组中p-Jak2和IL6的蛋白表达高于Sidt2 ^{+ / +}组。Sidt2 ^-/- + LPS组中p-Jak2和IL6的表达高于Sidt2 ^-/-组。Sidt2 ^-/- + LPS组中p-Jak2和IL6的表达高于Sidt2 ^{+ / +} + LPS组。Sidt2 ^{+ / +} + LPS组的MAPK途径中p-JNK，p-ERK，p-P38和ERK的表达高于Sidt2 ^{+ / +}组。Sidt2 ^-/- + LPS组中p-JNK，p-ERK，p-P38和ERK的表达高于Sidt2 ^-/-组。Sidt2 ^-/- + LPS组中p-JNK，p-ERK，p-P38和ERK的表达高于Sidt2 ^{+ / +} + LPS组。这些数据表明，Sidt2基因的缺失改变了三种炎症信号通路，最终导致了小鼠肾小球系膜细胞的损伤。