Overexpression of SGLT2 in the kidney of a P. gingivalis LPS-induced diabetic nephropathy mouse model.

Overexpression of SGLT2 in the kidney of a P. gingivalis LPS-induced diabetic nephropathy mouse model.
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DOI:
10.1186/s12882-021-02506-8
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发表时间:
2021-08-23
期刊:
影响因子:
2.3
通讯作者:
Sawa Y
Sawa Y
中科院分区:
医学4区
文献类型:
--
作者:
Kajiwara K;Sawa Y

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据报道,糖尿病肾脏中钠 - 葡萄糖协同转运蛋白2(SGLT2)过度表达。也已确定糖尿病肾小球内皮表达Toll样受体TLR2和TLR4。本研究旨在检测Toll样受体2/4配体牙龈卟啉单胞菌(P.)脂多糖(Pg - LPS)在小鼠糖尿病肾病中对肾脏SGLT2的诱导作用。 对链脲佐菌素(STZ)诱导的糖尿病ICR小鼠(STZ - ICR)、给予Pg - LPS的健康ICR小鼠(LPS - ICR)以及Pg - LPS诱导肾病的糖尿病ICR小鼠肾脏(LPS - STZ)进行免疫组织化学研究和组织RT - PCR分析。 在血糖水平的定量分析中,LPS - STZ组达到600mg/dl的平均时间比STZ - ICR组更短。LPS - STZ组血糖水平的升高比STZ - ICR组明显更陡。根据这些数据,LPS - STZ模型显示出明显的葡萄糖不耐受。SGLT2在LPS - STZ组整个肾实质中的表达比LPS - ICR组或STZ - ICR组明显更强。在LPS - STZ组肾脏的肾小管内和肾小管周围以及肾小球中均观察到SGLT2的表达。通过组织实时PCR和细胞ELISA分析,SGLT2基因和蛋白质在LPS - STZ组中的表达比LPS - ICR组或STZ - ICR组明显更强。LPS - ICR组和STZ - ICR组肾脏中肾脏SGLT2的产生没有差异。 在伴有牙龈卟啉单胞菌LPS的糖尿病肾脏中,SGLT2出现异常高的肾脏表达。牙周炎可能是糖尿病肾病以及糖尿病的一个加重因素。
The overexpression of sodium-glucose cotransporter 2 (SGLT2) in diabetic kidneys has been reported. It has also been established that the diabetic glomerular endothelium expresses the toll-like receptors TLR2 and TLR4. The present study aims to examine the renal SGLT2 induction by the TLR2/4 ligand Porphyromonas (P.) gingivalis lipopolysaccharide (Pg-LPS) in mouse diabetic nephropathy. Immunohistochemical study and tissue RT-PCR analyses were performed on mouse kidneys in streptozotocin (STZ)-induced diabetic ICR mice (STZ-ICR), in healthy ICR mice administered Pg-LPS (LPS-ICR), and in diabetic ICR mouse kidneys with Pg-LPS-induced nephropathy (LPS-STZ). In the quantitative analysis of blood sugar levels, the mean time to reach 600 mg/dl was shorter in the LPS-STZ than in the STZ-ICR kidneys. The rise in blood glucose levels was significantly steeper in the LPS-STZ than in the STZ-ICR kidneys. According to these data the LPS-STZ model suggests a marked glucose intolerance. The expression of SGLT2 was significantly stronger in the whole of the renal parenchyma of the LPS-STZ than in the LPS-ICR or in the STZ-ICR. The expression of SGLT2 was observed both in the renal tubules and around the renal tubules, and in the glomeruli of the LPS-STZ kidneys. In the analysis by tissue real-time PCR and cell ELISA, the expression of the SGLT2 gene and protein was significantly stronger in the LPS-STZ than in the LPS-ICR or in the STZ-ICR. There were no differences in the renal SGLT2 production in the LPS-ICR and the STZ-ICR kidneys. Abnormally high renal expression of SGLT2 occurs in diabetic kidneys with P. gingivalis LPS. Periodontitis may be an exacerbating factor in diabetic nephropathy as well as in diabetes.
DOI: 10.1016/s1532-3382(12)70006-4
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