When we treated rat bone marrow stromal cells (rBMSCs) with neuronal differentiation induction media, typical unfolded protein response (UPR) was observed. BIP/GRP78 protein expression was time-dependently increased, and three branches of UPR were all activated. ATF6 increased the transcription of XBP1 which was successfully spliced by IRE1. PERK was phosphorylated and it was followed by eIF2α phosphorylation. Transcription of two downstream targets of eIF2α, ATF4 and CHOP/GADD153, were transiently up-regulated with the peak level at 24 h. Immunocytochemical study showed clear coexpression of BIP and ATF4 with NeuN and Map2, respectively. UPR was also observed during the neuro-

a b s t r a c tAdipocytes are continuously stimulated by proinflammatory cytokines such as TNFa, which cause adipocyte dysfunction by facilitating the inflammatory response. Although miR-130 was reported to be an important regulator of adipogenesis by targeting PPARc mRNA, little is known about the mechanisms regulating miR-130 expression during the proinflammatory response. Here, we examined miR-130 levels in white adipose tissue (WAT) from high-fat diet (HFD) mice and TNFa-stimulated adipocytes. Primary transcripts of miR-130 were increased after TNFa stimulation, indicating that induction of miR-130 during the pro-inflammatory response is regulated by a transcriptional event. A chromatin immunoprecipitation assay showed that p65 binding to the promoter regions of miR-130 was enhanced after TNFa treatment. Taken together, our findings suggest that induction of miR-130 by TNFa is responsible for adipocyte dysfunction.

Background/Aims: Apoptosis contributes to cyclosporine (CsA)-induced renal cell death. This study tested the effects of CsA-induced endoplasmic reticulum (ER) stress on apoptotic cell death in an experimental model of chronic CsA nephropathy. Methods: CsA (15 mg/kg per day) was given to rats for 7 or 28 days. The ER stress response was evaluated with BiP expression, and the proapoptotic response was assessed with CHOP and caspase 12 expression. ER structure was evaluated by transmission electron microscopy, and apoptotic cell death was detected with TUNEL staining. Results: Short-term treatment of CsA for 7 days activated both the ER stress response (induction of BiP mRNA and protein) and the proapoptotic response (upregulation of caspase 12 and CHOP mRNAs and proteins). However, long-term treatment with CsA for 28 days decreased BiP and further increased CHOP. The imbalance between the two responses coincided with the timing of the appearance of apoptotic cell death and the disruption of the ER structure. Conclusion: Prolonged CsA-induced ER stress causes apoptotic cell death by depleting molecular chaperones and activating the proapoptotic pathway.

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a b s t r a c tDifferentiation of preadipocytes into adipocytes is controlled by various transcription factors. Recently, the pro-adipogenic function of XBP1, a transcription factor upregulated by endoplasmic reticulum stress, has been reported. In this study, we demonstrated that XBP1 suppresses the expression of Wnt10b, an anti-adipogenic Wnt, during the differentiation of 3T3-L1 preadipocytes. The expression pattern of XBP1 was reciprocal to that of Wnt10b during the early stage of adipogenesis. The intracellular protein levels of b-catenin were negatively regulated by XBP1. Direct binding of XBP1 to the Wnt10b promoter and the subsequent decrease of the b-catenin signalling pathway represent a novel adipogenic differentiation mechanism.