Background: Staphylococcus epidermidis(SE) has emerged as one of the most important causes of nosocomial infections. The SaeRS two-component signal transduction system (TCS) influences virulence and biofilm formation inStaphylococcus aureus. The deletion ofsaeRinS. epidermidisresults in impaired anaerobic growth and decreased nitrate utilization. However, the regulatory function of SaeRS on biofilm formation and autolysis inS. epidermidisremains unclear.Results: ThesaeRSgenes of SE1457 were deleted by homologous recombination. ThesaeRSdeletion mutant, SE1457ΔsaeRS, exhibited increased biofilm formation that was disturbed more severely (a 4-fold reduction) by DNase I treatment compared to SE1457 and the complementation strain SE1457saec. Compared to SE1457 and SE1457saec, SE1457ΔsaeRSshowed increased Triton X-100-induced autolysis (approximately 3-fold) and decreased cell viability in planktonic/biofilm states; further, SE1457ΔsaeRSalso released more extracellular DNA (eDNA) in the biofilms. Correlated with the increased autolysis phenotype, the transcription of autolysis-related genes, such asatlEandaae, was increased in SE1457ΔsaeRS. Whereas the expression of accumulation-associated protein was up-regulated by 1.8-fold in 1457ΔsaeRS, the expression of an N-acetylglucosaminyl transferase enzyme (encoded byicaA) critical for polysaccharide intercellular adhesin (PIA) synthesis was not affected by the deletion ofsaeRS.Conclusions: Deletion ofsaeRSinS. epidermidisresulted in an increase in biofilm-forming ability, which was associated with increased eDNA release and up-regulated Aap expression. The increased eDNA release from SE1457ΔsaeRSwas associated with increased bacterial autolysis and decreased bacterial cell viability in the planktonic/biofilm states.

The impact of Tim-3 (T cell immunoglobulin and mucin domain-containing protein 3) on cisplatin-induced acute kidney injury was investigated in this study. Cisplatin-induced Tim-3 expression in mice kidney tissues and proximal tubule-derived BUMPT cells in a time-dependent manner. Compared with wild-type mice, Tim-3 knockout mice have higher levels of serum creatinine and urea nitrogen, enhanced TUNEL staining signals, more severe 8-OHdG (8-hydroxy-2’ -deoxyguanosine) accumulation, and increased cleavage of caspase 3. The purified soluble Tim-3 (sTim-3) protein was used to intervene in cisplatin-stimulated BUMPT cells by competitively binding to the Tim-3 ligand. sTim-3 obviously increased the cisplatin-induced cell apoptosis. Under cisplatin treatment conditions, Tim-3 knockout or sTim-3 promoted the expression of TNF-α (tumor necrosis factor-alpha) and IL-1β (Interleukin-1 beta) and inhibited the expression of IL-10 (interleukin-10). NF-κB (nuclear factor kappa light chain enhancer of activated B cells) P65 inhibitor PDTC or TPCA1 lowed the increased levels of creatinine and BUN (blood urea nitrogen) in cisplatin-treated Tim-3 knockout mice serum and the increased cleavage of caspase 3 in sTim-3 and cisplatin-treated BUMPT cells. Moreover, sTim-3 enhanced mitochondrial oxidative stress in cisplatin-induced BUMPT cells, which can be mitigated by PDTC. These data indicate that Tim-3 may protect against renal injury by inhibiting NF-κB-mediated inflammation and oxidative stress.

Cisplatin nephrotoxicity has been considered as serious side effect caused by cisplatin‐based chemotherapy. Recent evidence indicates that renal tubular cell apoptosis and inflammation contribute to the progression of cisplatin‐induced acute kidney injury (AKI). Hepatocyte nuclear factor 1β (HNF1β) has been reported to regulate the development of kidney cystogenesis, diabetic nephrotoxicity, etc However, the regulatory mechanism of HNF1β in cisplatin nephrotoxicity is largely unknown. In the present study, we examined the effects of HNF1β deficiency on the development of cisplatin‐induced AKI in vitro and in vivo. HNF1β down‐regulation exacerbated cisplatin‐induced RPTC apoptosis by indirectly inducing NF‐κB p65 phosphorylation and nuclear translocation. HNF1β knockdown C57BL/6 mice were constructed by injecting intravenously with HNF1β‐interfering shRNA and PEI. The HNF1β scramble and knockdown mice were treated with 30 mg/kg cisplatin for 3 days to induce acute kidney injury. Cisplatin treatment caused increased caspase 3 cleavage and p65 phosphorylation, elevated serum urea nitrogen and creatinine, and obvious histological damage of kidney such as fractured tubules in control mice, which were enhanced in HNF1β knockdown mice. These results suggest that HNF1β may ameliorate cisplatin nephrotoxicity in vitro and in vivo, probably through regulating NF‐κB signalling pathway.

Cell migration is important for renal recovery from tubular cell injury. Heat shock transcription factor 1 (HSF1) is a well-studied regulatory factor that is active during acute kidney injury. HSF1 is also involved in the migration process during tumor metastasis. Therefore, we hypothesized that HSF1 may promote the recovery of renal function by affecting kidney tubular cell migration. A wound healing assay was used to examine the cell migration rate. The results demonstrated that the migration of rat kidney proximal tubular cells (RPTCs) was increased following knockdown of HSF1. In addition, the invasion ability of HSF1 knockdown RPTCs was also significantly upregulated. The present study also identified that transforming growth factor-beta 1 (TGF-beta 1) was highly expressed at the edge of the wound in control cells, and its expression was further increased upon knockdown of HSF1. Inhibition of TGF-beta 1 signaling prevented RPTC HSF1 knockdown cell migration, suggesting that HSF1-regulated RPTC cell migration was dependent on the TGF-beta 1 signaling pathway. Furthermore, phosphorylation of TGF-beta 1 and Smad2/3 was induced in HSF1 knockdown cells. Together, these results suggest that HSF1 may suppress RPTC migration by inhibiting the activation of the TGF-beta 1-Smad2/3 signaling pathway.