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This study investigated genome-wide gene expressions and the cardioprotective effects of electro-acupuncture pretreatment at the PC6 Neiguan acupoint on myocardial ischemia reperfusion (I/R) injury. Male SD rats were randomly divided into four groups: sham operation (SO), I/R, electro-acupuncture at the PC6 Neiguan acupoint pretreatment (EA) and electro-acupuncture at non-acupoint pretreatment (NA). Compared with the I/R group, the survival rate of the EA group was significantly increased, the arrhythmia score, infarction area, serum concentrations of CK, LDH and CK-Mb and plasma level of cTnT were significantly decreased. RNA-seq results showed that 725 genes were up-regulated and 861 genes were down-regulated under I/R conditions compared to the SO group; both EA and NA reversed some of these gene expression levels (592 in EA and 238 in NA group). KEGG pathway analysis indicated that these genes were involved in multiple OPEN ACCESSMolecules 2014, 19 16159 pathways, including ECM, MAPK signaling, apoptosis, cytokine and leukocyte pathways. In addition, some pathways were uniquely regulated by EA, but not NA pretreatment, such as oxidative stress, cardiac muscle contraction, gap junction, vascular smooth muscle contraction, hypertrophic, NOD-like receptor, and P53 and B-cell receptor pathways. This study was first to reveal the gene expression signatures of acute myocardial I/R injury and electro-acupuncture pretreatment in rats.

BackgroundAcupuncture exerts cardioprotective effects on several types of cardiac injuries, especially myocardial ischemia (MI), but the mechanisms have not yet been well elucidated. Angiogenesis mediated by VEGF gene expression and its modification through histone acetylation has been considered a target in treating myocardial ischemia. This study aims to exam whether modulation of angiogenesis through H3K9 acetylation regulation at VEGF gene is one possible cardioprotective mechanism of acupuncture.ResultsWe generated rat MI models by ligating the left anterior descending coronary artery and applied electroacupuncture (EA) treatment at the Neiguan (PC6) acupoint. Our results showed that acupuncture reversed the S-T segment change, reduced Q-wave area, decreased CK, CK-MB, LDH levels, mitigated myocardial remodeling, and promoted microvessel formation in the MI heart. RNA-seq analysis showed that VEGF-induced angiogenesis signaling was involved in the modulation of EA. Western blot results verified that the protein expressions of VEGF, Ras, phospho-p44/42 MAPK, phospho-p38 MAPK, phospho-SAPK/JNK and Akt, were all elevated significantly by EA treatment in the MI heart. Furthermore, increased H3K9 acetylation was also observed according with the VEGF. ChIP assay confirmed that EA treatment could notably stimulate the recruitment of H3K9ace at the VEGF promoter.ConclusionsOur study demonstrates for the first time that acupuncture can effectively up-regulate VEGF expression through H3K9 acetylation modification directly at the VEGF promoter and hence activate VEGF-induced angiogenesis in rat MI models. We employed high throughput sequencing in this study and, for the first time, generated genome-wide gene expression profiles both in the rat MI model and in acupuncture treatment.

MicroRNAs are a kind of small non-coding RNAs that play important roles in various biological processes such as cell proliferation, differentiation, and apoptosis. Cellular responses to UV-induced apoptosis have been suggested to be regulated by microRNAs at the posttranscriptional level, while the detailed mechanisms underlying this process remain unclear. Our aim in this study was to investigate the effects of miR-1246 in UVB-induced apoptosis and to identify the functional targets of miR-1246 in keratinocyte HaCaT cells. The expression of miR-1246 and apoptotic genes in HaCaT cells experiencing UVB stress was determined using quantitative real-time PCR. miR-1246 functions in UVB-induced apoptosis were quantified via fluorescence-activated cell sorter analysis of miR-1246 mimic or inhibitor-transfected cells. Additionally, the regulatory relationship between RTKN2 and miR-1246 was identified by Western blot and luciferase reporter assays. miR-1246 was upregulated accompanying with UVB-irradiated apoptosis in HaCaT cells. Overexpression of miR-1246 promoted UVB-induced apoptosis, while knockdown of miR-1246, using a specific inhibitor, resulted in a significant reduction in UVB-elicited apoptosis. We further demonstrate that miR-1246 negatively regulated the expression of RTKN2 through binding to the 3'-untranslated region of RTKN2 at the posttranscriptional level. Moreover, RTKN2 was observed to be resistant to UVB-induced apoptosis and RTKN2 antagonized the pro-apoptotic effects of miR-1246 during UVB-induced apoptosis in HaCaT cells. These findings suggested that miR-1246 promotes UVB-induced apoptosis by downregulating RTKN2 expression and that UVB-upregulated miR-1246 released RTKN2-dependent resistance to UVB-induced apoptosis by targeting RTKN2 post-transcriptionally in keratinocyte cells.

These results indicate that the GZFL capsule can induce apoptosis of endometriotic cells and inhibit cell proliferation and metastasis of endometriotic cells through the mitochondrial apoptotic pathway.