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

• Published in: BMC nephrology 2021-08, Vol.22 (1), p.287-287, Article 287
• Main Authors: Kajiwara, Koichiro, Sawa, Yoshihiko
• Format: Article
• Language: English
• Subjects: Animals; Blood Glucose - analysis; Carrier proteins; Collagen; Creatinine; Cytokines; Development and progression; Diabetes; Diabetes mellitus; Diabetes Mellitus, Experimental - metabolism; Diabetic nephropathies; Diabetic Nephropathies - metabolism; Diabetic nephropathy; Endothelium; Enzyme-Linked Immunosorbent Assay; Experiments; Gene expression; Genetic aspects; Glucose; Glucose tolerance; Health aspects; Hyperglycemia; Immunohistochemistry; Intolerance; Kidney - metabolism; Kidneys; Lipopolysaccharides; LPS; Male; Mice; Microorganisms; Na+/glucose cotransporter; Nephrology; Nephropathy; P. gingivalis; Parenchyma; Pathogens; Periodontitis; Polymerase chain reaction; Porphyromonas gingivalis; Proteins; Real-Time Polymerase Chain Reaction; Renal tubules; Risk factors; RNA, Messenger - metabolism; SGLT2; Sodium-Glucose Transporter 2 - genetics; Sodium-Glucose Transporter 2 - metabolism; Streptozocin; TLR2 protein; TLR4 protein; Toll-like receptors; Urine
• ISSN: 1471-2369; 1471-2369
• DOI: 10.1186/s12882-021-02506-8

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.