BackgroundLipotoxicity is a key feature of the pathogenesis of diabetic kidney disease, and is attributed to excessive lipid accumulation (hyperlipidemia). Increasing evidence suggests that fibroblast growth factor (FGF)21 has a crucial role in lipid metabolism under diabetic conditions.ObjectiveThe present study investigated whether FGF21 can prevent hyperlipidemia- or diabetes-induced renal damage, and if so, the possible mechanism.MethodsMice were injected with free fatty acids (FFAs, 10 mg/10 g body weight) or streptozotocin (150 mg/kg) to establish a lipotoxic model or type 1 diabetic model, respectively. Simultaneously the mice were treated with FGF21 (100 µg/kg) for 10 or 80 days. The kidney weight-to-tibia length ratio and renal function were assessed. Systematic and renal lipid levels were detected by ELISA and Oil Red O staining. Renal apoptosis was examined by TUNEL assay. Inflammation, oxidative stress, and fibrosis were assessed by Western blot.ResultsAcute FFA administration and chronic diabetes were associated with lower kidney-to-tibia length ratio, higher lipid levels, severe renal apoptosis and renal dysfunction. Obvious inflammation, oxidative stress and fibrosis also observed in the kidney of both mice models. Deletion of the fgf21 gene further enhanced the above pathological changes, which were significantly prevented by administration of exogenous FGF21.ConclusionThese results suggest that FFA administration and diabetes induced renal damage, which was further enhanced in FGF21 knock-out mice. Administration of FGF21 significantly prevented both FFA- and diabetes-induced renal damage partially by decreasing renal lipid accumulation and suppressing inflammation, oxidative stress, and fibrosis.

Long non-coding RNAs (lncRNAs) play vital roles in diabetic nephropathy (DN). This research aimed to study the potential role and underlying molecular mechanisms of long non-coding RNA MEG3 in DN. We found that MEG3 was upregulated in DN in vivo and in vitro and could enhance cell fibrosis and inflammatory response in DN. MEG3 functioned as an endogenous sponge for miR-181a in mesangial cells (MCs) via direct targeting and in an Ago2-dependent manner. MiR-181a inhibition promoted MC fibrosis and inflammatory response. In addition, Egr-1 was confirmed as a target gene of miR-181a. Further investigations verified that MEG3 promotes fibrosis and inflammatory response via the miR-181a/Egr-1/TLR4 axis in vitro and in vivo. These results provide new insights into the regulation between MEG3 and the miR-181a/Egr-1/TLR4 signaling pathway during DN progression.

One-sentence summary: SAUR17 is highly expressed in apical hooks and cotyledons in the dark, where it promotes etiolation by protecting the phosphatase activity of PP2C-D1 against cell-expansion-inducing SAURs such as SAUR50.

Epstein-Barr virus (EBV) is a known tumor virus associated with an increasing array of malignancies; however, the association of the virus with certain malignancies is often erratic. To determine EBV’s contributions to tumorigenesis in a setting of incomplete association, a transient model of infection was established where a clonal CCL185 carcinoma cell line infected with recombinant EBV was allowed to lose viral genomes by withdrawal of selection pressure. Global gene expression comparing EBV-negative, transiently infected clones to uninfected controls identified expression changes in over 1000 genes. Among downregulated genes, several genes known to be DNA methylated in cancer were identified including E-cadherin and PYCARD. A cadherin switch, increased motility and enhanced cellular invasiveness present in EBV-positive cells were retained following viral loss indicating an epigenetic effect. Repression of PYCARD expression was due to increased promoter CpG methylation, whereas loss of E-cadherin expression after transient EBV infection did not correlate with increased DNA methylation of the E-cadherin promoter. Rather, repression of E-cadherin was consistent with formation of a repressive chromatin state. Decreased histone 3 or 4 acetylation at the promoter and 5’ end of the E-cadherin gene was observed in an EBV-negative, transiently infected clone relative to the uninfected controls. These results suggest that EBV can stably alter gene expression in a heritable fashion in formerly infected cells, while its own contribution to the oncogenic process is masked.