Abstract
Diabetic nephropathy is a common complication in diabetes, but still lack of effective therapeutic strategies. This study aimed to investigate the therapeutic effect of basic fibroblast growth factor (bFGF) in db/db mice with diabetic nephropathy and explore its possible metabolic mechanisms using a nuclear magnetic resonance-based metabolomic approach. We found that bFGF treatment significantly alleviate urinary albumin to creatinine ratio and renal fibrosis in db/db mice, suggesting a potential renal protective effect. Metabolomics results reveal that bFGF remodeled metabolic phenotypes of the kidney and urine in db/db mice, mainly involving energy metabolism, methylamine metabolism, osmoregulation, and oxidative stress. Furthermore, the results show that bFGF-induced reductions of oxidative stress and apoptosis in db/db mice might be mediated by NOX-ROS-Nrf2 signaling. Therefore, our study suggests that the protective effect of bFGF on diabetic nephropathy could be mediated by remodeling metabolic phenotype and suppressing oxidative stress.
Highlights
Diabetic nephropathy (DN) is one of the most common microvascular complications of diabetes and has become the leading cause of end-stage renal failure and death of both type I and II diabetic patients (Yu and Bonventre, 2018; Wang et al, 2019)
The result shows that the urinary albumin to creatinine ratio (UACR) level was significantly increased in db/db mice compared with age-matched wt mice (Figure 1G), whereas basic fibroblast growth factor (bFGF) treatment significantly decreased its level in db/db mice
We found that the levels of creatinine, citrate, ATP, fumarate, TMAO, DMA, and myo-inositol were significantly increased in db/db mice compared with agematched wt mice, but these increased trends were significantly reduced after bFGF treatment (Figure 6)
Summary
Diabetic nephropathy (DN) is one of the most common microvascular complications of diabetes and has become the leading cause of end-stage renal failure and death of both type I and II diabetic patients (Yu and Bonventre, 2018; Wang et al, 2019). Basic fibroblast growth factor (bFGF), a member of the growth factor family, has been reported to reduce the functional and morphological damages in chronic kidney disease and induce the re-expression of nephrogenic/ angiogenic factors (Villanueva et al, 2014). BFGF treatment can effectively reduce serum glucose and lipid levels in STZinduced diabetic rats and prevent DN through inhibition of inflammation (Lin et al, 2016; Sheng et al, 2018). The metabolic mechanisms of bFGF on diabetic kidney diseases remain unclear
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