Biological role(s) of Fc gammaRI on mouse primary sensory neurons are not fully understood. Sensory neuron stimulation increases insulin-like growth factor-I (IGF-I) production, thereby reducing ischemia/reperfusion (I/R)-induced tissue injury in mice. In this study, we examined whether the Fc fragment of IgG (IgGFc) increases IGF-I production through sensory neuron stimulation, thereby reducing I/R-induced renal injury in mice. IgGFc increased the calcitonin-gene-related peptide (CGRP) release and cellular cAMP levels in dorsal root ganglion neurons isolated from wild-type (WT) mice, whereas, native IgG did not. Pretreatment with anti-Fc gammaRI Ab, a protein kinase A inhibitor KT5710, and a phospholipase A(2) inhibitor 4-bromophenylacyl bromide inhibited these effects induced by IgGFc. Administration of IgGFc enhanced increases of renal tissue levels of CGRP and IGF-I and reduced I/R-induced renal injury in WT mice. Increases of renal tissue level of caspase-3, renal accumulation of neutrophils, and renal tubular apoptosis were inhibited by administration of IgGFc in WT mice subjected to renal I/R. Pretreatment with anti-IGF-I Ab completely reversed these effects induced by IgGFc in WT mice. Administration of native IgG did not show any effects in WT mice subjected to renal I/R. None of the effects observed in WT mice was seen after IgGFc administration in CGRP-knockout mice and denervated WT mice. These observations suggest that activation of Fc gammaRI by IgGFc may stimulate sensory neurons, thereby promoting IGF-I production, contributing to reduction of the reperfusion-induced renal injury via attenuation of inflammatory responses in mice.
Objective To explore the effects of extracellular signal-regulated kinase1 (ERK1) small interfering RNA on the biological characteristics of rat hepatoma cells and its possible mechanism.Methods The expressions of ERK1 in hepatoma cell lines,primary rat hepatocyte,and 12 human hepatocellular carcinoma (HCC) specimens and their paired non-cancerous liver tissues were detected by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry staining.Hepatoma cell lines RH-35 and H4IIE cells were infected with extracellular signal-regulated kinase 1 by adenvirus mediated small interfering RNA (AdshERK1) or a scrambled small interfering RNA used as a negative control which was mediated by adenvirus (AdshNC).After the expression of ERK1 in hepatoma cells downregulated,the effects on its biological characteristics and the changes of its downstream oncogene expression were detected.The data were analyzed by t test.Results Among 12 human HCC specimens,the expressions of ERK1 in 11 specimens were higher than those of corresponding adjacent tissues.Compared with primary hepatocytes,the expressions of ERK1 in rat hepatoma cell lines RH 35 and H4IIE upregulated (0.016±0.003 vs 0.075±0.010,0.458±0.052;t=13.806 and 7.715,both P＜0.01).After RH-35 and H4IIE cells transfected with AdshERK1,the ability of cell proliferation and colony formation were suppressed.Compared with AdshNC,AdshERK1 transfection could significantly decrease the percentage of S phase cells(18.55％ ±4.80％ vs 4.39 ％ ± 0.85 ％,t =-6.826,P＜0.01),which caused G0/G1 phase of cell cycle arrest(76.77 ％ ±0.93％ vs 89.57％ ± 1.26％,t =11.676,P＜0.01) ; AdshERK1 significantly inhibited the tumor formation ability of H4IIE cells in nude mice [(0.603± 0.284) mg vs (0.051 ± 0.074) mg,t=-5.340,P＜ 0.01].AdshERK1 downregulated the expressions of ERK1 in RH-35 and H4IIE cells and suppressed the expressions of downstream oncogene c-myc.Conclusions AdshERK1 has the role of inhibiting cell proliferation,colony and tumor formation ability of RH-35 and H4IIE cells.This role may be closely related with inhibiting the expression of its downstream oncogene c-myc.
Key words:
Carcinoma, hepatocellular; Mitogen-activated protein kinase 3; RNA, small interfering; Genes, myc; Tumor cells, cultured
Summary The global transition towards diets high in calories has contributed to 2.1 billion people becoming overweight, or obese, which damages male reproduction and harms offspring. Recently, more and more studies have shown that paternal exposure to stress closely affects the health of offspring in an intergenerational and transgenerational way. SET Domain Containing 2 ( SETD 2 ), a key epigenetic gene, is highly conserved among species, is a crucial methyltransferase for converting histone 3 lysine 36 dimethylation (H3K36me2) into histone 3 lysine 36 trimethylation (H3K36me3), and plays an important regulator in the response to stress. In this study, we compared patterns of SETD2 expression and the H3K36me3 pattern in pre-implantation embryos derived from normal or obese mice induced by high diet. The results showed that SETD 2 mRNA was significantly higher in the high-fat diet (HFD) group than the control diet (CD) group at the 2-cell, 4-cell, 8-cell, and 16-cell stages, and at the morula and blastocyst stages. The relative levels of H3K36me3 in the HFD group at the 2-cell, 4-cell, 8-cell, 16-cell, morula stage, and blastocyst stage were significantly higher than in the CD group. These results indicated that dietary changes in parental generation (F0) male mice fed a HFD were traceable in SETD 2/H3K36me3 in embryos, and that a paternal high-fat diet brings about adverse effects for offspring that might be related to SETD2/H3K36me3, which throws new light on the effect of paternal obesity on offspring from an epigenetic perspective.
Cervical cancer (CC) is a major health threat to women worldwide. Long non-coding RNA (lncRNA) has been reported to play crucial roles in regulating carcinogenesis, including CC.In this work, levels of lncRNA forkhead box P4 antisense RNA 1 (FOXP4-AS1) in CC cell lines and normal cell lines were analyzed with quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) method. Effects of FOXP4-AS1 on CC cellular behaviors including proliferation, migration, and invasion were explored. Bioinformatic prediction tools and luciferase activity reporter assay were conducted to explore the downstream molecules for FOXP4-AS1.We found FOXP4-AS1 expression was significantly higher in CC cell lines than in normal cell line. Functionally, force FOXP4-AS1 expression increased CC cell proliferation, migration, and invasion, while FOXP4-AS1 knockdown caused opposite effects. Mechanistically, we found FOXP4-AS1 acts as competing endogenous RNA (ceRNA) for microRNA-136-5p (miR-136-5p) to regulate chromobox 4 (CBX4) expression.These findings indicated FOXP4-AS1 plays an oncogenic role in CC, which may provide novel therapeutic biomarker against CC.
Objective To explore the expressions and co-relationship of immune factors forkhead box p3 (FoxP3),chemokine (C-C motif) ligand 22 (CCL22),tumor necrosis factor receptor superfamily member 40(OX40),and SMAD family member 3 (Smad3) in cervical carcinoma and investigate their immunomodulatory roles in cervical carcinogenesis.Methods Totally 30 cases of cervical carcinoma with adjacent tissues and 20 cases of normal cervix were collected in this study. FoxP3,CCL22,OX40,and Smad3 mRNA expressions were detected by real-time polymerase chain reaction (RT-PCR). Results Compared to normal cervix,the expression levels of FoxP3 and CCL22 mRNA were elevated in neoplastic foci(P=0.000,P=0.002) and tumor periphery (P=0.048,P=0.040).The mRNAs increased modestly in high-grade squamous cell carcinoma focal(P=0.019,P=0.020) and periphery tissue (P=0.023,P=0.031) in comparison with low-grade squamous cell carcinoma. The expression levels of OX40 and Smad3 mRNA were significantly lower in neoplastic foci(P=0.000,P=0.015) than normal cervix. Compared to low-grade squamous cell carcinoma focal and periphery tissue,the mRNAs decreased moderately in high-grade squamous cell carcinoma(P=0.018,P=0.030; P=0.027,P=0.014). In both neoplastic foci and tumor periphery,the mRNA expression level of CCL22 was positively correlated with FoxP3 (r=0.353,P=0.000; r=0.307,P=0.000) but negatively correlated with OX40 (r=-0.288,P=0.031; r=-0.263,P=0.037),while OX40 was positively correlated with Smad3 (r=0.384,P=0.002;r=0.288,P=0.023). The mRNA expressions of FoxP3 and CCL22 were increased in foci and pericarcinous tissues (P=0.024,P=0.039; P=0.032,P=0.034) while Smad3 was decreased in neoplastic foci (P=0.017) in contrast to HPV negative corresponding group. Conclusion FoxP3 and CCL22 expressions increase while OX40 and Smad3 expression decrease at mRNA level in the microenvironment of cervical cancer,which may be associated with such immunological model that the immunosuppressive roles of FoxP3 and CCL22 enhance while the immunity-boosting roles of OX40 and Smad3 are impeded,contributing to the deterioration of immune disequilibrium in local site and cervical cancer carcinogenesis.
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