The Hoxb7-Cre; Vhlhdel/del mice are renal tubule-specific conditional Vhlh gene-knockout C57BL/6 mice that spontaneously develop fibrosis, inflammation and hyperplastic clear-cell lesions in the kidney. Studies have shown that gamma-aminobutyric acid (GABA) is a potential therapeutic agent against the renal damage involved in acute renal failure in nephrectomized rats, and acts as a natural immunomodulator of T lymphocytes, but its effects on renal protection are still unclear. Therefore, we investigate the effects of GABA supplement on life span and renal mRNA expression in Vhlhdel/del mice with renal inflammation.
The Vhlhdel/del mice were fed with control diet (Con, n=9), GABA rice containing diet (G-rice, n=8), or pure GABA containing diet (GABA, n=10). The life span among these three groups of mice was followed. Serum levels of creatinine, BUN, C-reactive protein (CRP), TGF-beta and IL-6 were measured. The Vhlhdel/del mice from Con (n=2) and G-rice (n=2) groups were sacrificed for renal RNA sequencing analysis after 10-weeks’ diet treatment. The folds of gene expressions in kidney from the G-rice mice compared to the Con mice were analyzed. Cytokines secretions of mitogen-stimulated splenocytes were also measured.
The life span of mice in the G-rice and the GABA groups were significantly longer than those in the Con group. Serum creatinine and CRP levels in the G-rice mice were significantly lower than those in the Con mice. Mice fed with GABA rice had significantly increased the renal gene expression of a tumor suppressor gene, per2, and Jak-STAT signaling related genes, but decreased glutathione metabolism related genes. IL-17 secretion of mitogen-stimulated splenocytes was significantly higher in the G-rice group.
GABA rice supplement decreased the renal inflammation and injury, and thus increased the life span in the Vhlh gene knockout mice. GABA rice feeding might regulate the expression of several genes related to tumor formation and metabolic stress in kidney.