Experimental cell research
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Retracted Publication
Paracrine signaling by VEGF-C promotes non-small cell lung cancer cell metastasis via recruitment of tumor-associated macrophages.
High expression of tumoral vascular endothelial growth factor C (VEGF-C) is correlated with clinical non-small cell lung cancer (NSCLC) metastasis and patient survival. Nevertheless, the comprehensive mechanisms accounting for VEGF-C-mediated cancer progression remain largely unclear. The present study found that VEGF-C expression was upregulated in various NSCLC cell lines. ⋯ Finally, the functional importance of macrophage infiltration induced by tumoral VEGF-C in promoting metastasis was established in a mouse model. In conclusion, our results highlight a novel function of tumoral VEGF-C that paracrinely induces macrophage recruitment, and resultantly promotes NSCLC cell metastasis. Therefore, VEGF-C/VEGFR-2/3 axis may be a promising microenvironmental target against progression of NSCLC.
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Activation of hepatic stellate cells (HSCs) is an essential event in the initiation and progression of liver fibrosis. HSCs are believed to be the major source of collagen-producing myofibroblasts in fibrotic livers. A key feature in the pathogenesis of liver fibrosis is fibrillar Collagen I (Col 1) deposition. ⋯ Finally, miR-129-5p level was decreased in fibrotic liver of human, and reduced by rOPN treatment. In contrast, miR-129-5p was induced in HSCs transfected by OPN siRNA. These data suggested that OPN induces Col 1 expression via suppression of miR-129-5p in HSCs.
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Inflammatory modulation mediated by microglial M1/M2 polarization is one of the main pathophysiological processes involved in early brain injury (EBI) after subarachnoid haemorrhage (SAH). Previous studies have shown that recombinant human erythropoietin (rhEPO) alleviates EBI following experimental SAH. However, the mechanisms of this beneficial effect are still poorly understood. ⋯ Interestingly, the effect of EPO on microglia polarization was cancelled by EPOR knockdown or by p-JAK2 or p-STAT3 inhibition, suggesting a core role of the EPOR/JAK2/STAT3 pathway in modulating microglial function and phenotype. In conclusion, the therapeutic effect of rhEPO on the early brain injury after SAH may relate to its modulation of inflammatory response and microglia M1/M2 polarization, which may be mediated in part by the EPOR/JAK2/STAT3 signalling pathway. These results improved the understanding of the anti-inflammatory effect of EPO on microglia polarization, which might optimize the therapeutic modalities of EPO treatment with SAH.
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JMJD2A is a JmjC histone demethylase that catalyzes the demethylation of di- and trimethylated Lys9 and Lys36 in histone H3 (H3K9me2/3 and H3K36me2/3). The role of spinal JMJD2A-dependent histone demethylation in nociception hypersensitivity development remains elusive. Here we reported that the JMJD2A responded to neuropathic pain and participated in the maintenance of neuropathic pain. ⋯ JMJD2A bound to the promoter of Bdnf and demethylated H3K9me3 and H3K36me3 at Bdnf promoter to promote the expression of Bdnf. Finally, we showed that JMJD2A promoted the expression of Bdnf during neuropathic pain and neuron-specific knockout of Jmjd2a blocked the hypersensitivity of mice undergoing chronic neuropathic pain induced by CCI and SNI. Taken together, our findings demonstrate that up-regulation of JMJD2A promotes neuropathic pain and it may serve as a promising target for treatment of chronic neuropathic pain.
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Lung cancer remains a leading cause of cancer-related mortality, with metastatic progression remaining the single largest cause of lung cancer mortality. Hence it is imperative to determine reliable biomarkers for lung cancer prognosis. We performed quantitative real-time PCR (qRT-PCR) analysis to explore epithelial-mesenchymal transition (EMT) inducers that regulate EMT process in three patients with advanced lung cancer disease. ⋯ Upregulation of PPARGC1A transcript expression was independent of a differential upregulation of the upstream AMP-dependent protein kinase (AMPK) activation or steady state expression of the silent mating type information regulation 2 homolog 1 (SIRT1). Xenograft tail vein colonization assays proved that the high expression of PPARGC1A was a prerequisite for metastatic progression of lung cancer to brain. Our results indicate that PPARGC1A might be a potential biomarker for lung cancer prognosis.