Ischemia-reperfusion (I/R) is a common cause of acute kidney injury (AKI), which is associated with high mortality and poor outcomes. Autophagy plays important roles in the homeostasis of renal tubular cells (RTCs) and is implicated in the pathogenesis of AKI, although its role in the process is complex and controversial. Fibroblast growth factor 10 (FGF10), a multifunctional FGF family member, was reported to exert protective effect against cerebral ischemia injury and myocardial damage. Whether FGF10 has similar beneficial effect, and if so whether autophagy is associated with the potential protective activity against AKI has not been investigated. Herein, we report that FGF10 treatment improved renal function and histological integrity in a rat model of renal I/R injury. We observed that FGF10 efficiently reduced I/R-induced elevation in blood urea nitrogen, serum creatinine as well as apoptosis induction of RTCs. Interestingly, autophagy activation following I/R was suppressed by FGF10 treatment based on the immunohistochemistry staining and immunoblot analyses of LC3, Beclin-1 and SQSTM1/p62. Moreover, combined treatment of FGF10 with Rapamycin partially reversed the renoprotective effect of FGF10 suggesting the involvement of mTOR pathway in the process. Interestingly, FGF10 also inhibited the release of HMGB1 from the nucleus to the extracellular domain and regulated the expression of inflammatory cytokines such as TNF-α, IL-1β and IL-6. Together, these results indicate that FGF10 could alleviate kidney I/R injury by suppressing excessive autophagy and inhibiting inflammatory response and may therefore have the potential to be used for the prevention and perhaps treatment of I/R-associated AKI.

Aims: Clinical studies showed that the use of probiotics during critical illness reduced nosocomial infection and improved clinical outcome. However, the functional mechanisms of probiotics is remains unclear. Therefore the aim of current study is to explore the protective effects and understand the underlying mechanisms for the beneficial effects of live combined Bacillus subtilis and Enterococcus faecium (LCBE) in cecal ligation puncture (CLP)-induced sepsis.Methods and Results: Seven-week-old C57BL/6J mice were divided into three groups: sham group (6 mice), CLP-control group (20 mice, pretreatment with saline for 7 days before CLP surgery) and CLP-probiotics group (14 mice, pretreatment with LCBE enteric-coated capsules for 7 days before CLP surgery). In survival experiment, mice were monitored for 7 days after CLP. After the procedure, mice were sacrificed, and, serum, and peritoneal lavage fluid were collected and intestinal ileal samples were harvested.Results: Our results showed that the mortality was significantly reduced in mice CLP-probiotics group vs. CLP-control group (P < 0.05). Also, treatment CLP-probiotics group decreased the injury scores CLP-probiotics group when compared to CLP-control group. Additionally, levels of pro-inflammatory cytokines IL-6 and TNF-α levels in the serum and intestinal ileal tissues of CLP-probiotics group were reduced when compared to CLP-control group (P < 0.05). However, no significant differences in anti-inflammatory levels of IL-10 and TGF-β1 were observed between CLP-control and CLP-probiotic groups. Furthermore, our experiments showed that that probiotic treatment suppressed the macrophage activation and transformation from M-type to M1-type, inhibited the mast cells (MCs) degranulation, and activation of AKT (kinase B) pathway.Conclusion: In conclusion, our data shows that probiotics have a protective role in CLP septic mice through reducing intestinal inflammation, altering macrophage polarization and MCs degranulation, and regulating AKT signaling.Significance and Impact of Study: This study demonstrated the protective effects and mechanisms involved in the protective role of live combined Bacillus subtilis and Enterococcus faecium (LCBE) in CLP-induced septic mice model.