Expression Of Suppressor Of Cytokine Signaling 2 Research Articles

SOCS2 inhibits hepatoblastoma metastasis via downregulation of the JAK2/STAT5 signal pathway

Metastasis of hepatoblastoma (HB) is a key factor that impairs the prognosis and treatment of children. The suppressor of cytokine signaling 2 (SOCS2) is a classical negative feedback protein that regulates cytokine signal transduction and has been known to be downregulated in several tumor, but the molecular mechanisms of its involvement in HB metastasis are unknown. We found that SOCS2 was a gene down-regulated in hepatoblastoma and associated with HB metastasis through bioinformatics. The qRT-PCR, Western blot and IHC showed that SOCS2 was significantly lower in HB tissues. Clinicopathological correlation analysis revealed that low expression of SOCS2 was significantly correlated with tumor metastasis (P = 0.046) and vascular invasion (P = 0.028), associated with poor prognosis. Overexpression of SOCS2 inhibited the migration and invasion of hepatoblastoma cells, while knockdown of SOCS2 expression promoted these malignant phenotypes. In vivo studies revealed overexpression of SOCS2 inhibited the formation of lung metastasis. Up-regulation of SOCS2 in HB cell inhibited EMT and JAK2/STAT5. Conversely, down-regulation of SOCS2 promoted EMT and JAK2/STAT5. The addition of the JAK2 inhibitor Fedratinib partially reversed the effects of si-SOCS2 on HB cells. SOCS2 may inhibit the migration and invasion of HB cells by inhibiting the JAK2/STAT5 signaling pathway. These results may provide guiding significance for the clinical treatment of HB.

Comprehensive analysis of suppressor of cytokine signaling 2 protein in the malignant transformation of NSCLC.

Suppressor of cytokine signaling 2 (SOCS2) plays an essential role in a number of physiological phenomena and functions as a tumor suppressor. Understanding the predictive effects of SOCS2 on non-small cell lung cancer (NSCLC) is urgently needed. The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were used to assess SOCS2 gene expression levels in NSCLC. The clinical significance of SOCS2 was evaluated through Kaplan-Meier curve analysis and the analysis of related clinical factors. Gene Set Enrichment Analysis (GSEA) was used to identify the biological functions of SOCS2. Subsequently proliferation, wound-healing, colony formation and Transwell assays, and carboplatin drug experiments were used for verification. The results revealed that SOCS2 expression was low in the NSCLC tissues of patients in TCGA and GEO database analyses. Downregulated SOCS2 was associated with poor prognosis, as determined by Kaplan-Meier survival analysis (HR 0.61, 95% CI 0.52-0.73; P<0.001). GSEA showed that SOCS2 was involved in intracellular reactions, including epithelial-mesenchymal transition (EMT). Cell experiments indicated that knockdown of SOCS2 caused the malignant progression of NSCLC cell lines. Furthermore, the drug experiment showed that silencing of SOCS2 promoted the resistance of NSCLC cells to carboplatin. In conclusion, low expression of SOCS2 was associated with poor clinical prognosis by effecting EMT and causing drug resistance in NSCLC cell lines. Furthermore, SOCS2 could act as a predictive indicator for NSCLC.

Exploring novel independent prognostic biomarkers for hepatocellular carcinoma based on TCGA and GEO databases.

Hepatocellular carcinoma (HCC) has become the fifth most common cancer globally, with the second-highest mortality rate and poor survival outcomes. In our research, we aimed to use The Cancer Genome Atlas and gene expression omnibus databases to identify potential genetic biomarkers to predict and improve the survival rate of HCC patients. In GSE60502, GSE76427, and GSE84402, we performed differential expression analysis to obtain differentially expressed genes (DEGs). In the The Cancer Genome Atlas database, the FPKM expression profile was subjected to weighted gene co-expression analysis to obtain modules closely related to HCC. We received common genes by intersecting the genes in the module with the differential genes. Then, we fused the common genes' expression profiles, survival time, and survival status for univariate, Least Absolute Shrinkage and Selection Operator, and multivariate COX regression analysis to obtain prognostic genes. Predictive genes were performed in K-M survival analysis and combined with clinical data for independent predictive analysis. After differential expression analysis, GSE60502 obtained 1107 DEGs, GSE76427 obtained 424 DEGs, and GSE84402 obtained 1668 DEGs. Through weighted gene co-expression analysis analysis, we can see that the blue and brown modules were closely associated with HCC. After single and multivariate COX regression analysis, we found that suppressor of cytokine signaling 2 (SOCS2) and SERPINF2 were independent prognostic genes for HCC. After survival analysis, HCC patients with high expression of SOCS2 and SERPINF2 had a longer survival time. These 2 genes in normal liver tissues were higher than in HCC at the transcriptional level. SOCS2 and SERPINF2 were new independent prognostic genes of HCC. So, they may provide new treatment methods and measures for diagnosing HCC.

Targeting signaling pathways vulnerabilities for the treatment of IKZF1-deleted ph-negative B lymphoblastic leukemia.

7033 Background: Approximately 20% of children diagnosed with B lymphoblastic leukemia (B-ALL) will suffer a relapse, and most adults with B-ALL have a poor prognosis. Genome-wide association studies of B-ALL patients have identified frequent deletions of the gene IKZF1, encoding the master regulator of lymphoid development, IKAROS. These deletions are associated with therapy resistance, increased risk of relapse, and inferior survival. Currently, how loss of IKAROS function contributes to therapy resistance and increased risk of relapse is not fully understood. We used CRISPR-Cas9 genome editing to develop human B-ALL cell lines with various IKZF1 deletions that genetically and phenotypically recapitulate those occurring in patients. Using these isogenic cell lines, we have previously shown IKZF1 deletion results in cell-intrinsic chemoresistance and increased activation of the JAK/STAT signaling pathway (Rogers, Gupta et al. 2021). Methods: Given JAK/STAT is often dysregulated in poor-prognosis leukemia, we investigated the potential mechanisms of aberrant JAK/STAT activation and the therapeutic potential of targeting JAK/STAT in our engineered cell lines. We treated our cells with SH-4-54 (STAT3/5 inhibitor) or tofacitinib (JAK1 inhibitor) alone and in combination with dexamethasone. To elucidate how loss of IKAROS mediates an increase in JAK-STAT activity, we also performed RNAseq of known pathway regulators, comparing IKZF1 wild-type with IKZF1 knockout. Results: The JAK/STAT negative regulator Suppressor of Cytokine Signaling 2 (SOCS2) was significantly downregulated with IKZF1 deletion, validated by RTqPCR and immunoblotting. We further analyzed publicly-available RNAseq data from &gt; 650 pediatric B-ALL samples, finding that SOCS2 expression is significantly lower in patients with low IKZF1expression (likely corresponding to IKZF1 deletion) compared to those with high IKZF1 expression. When we treated our engineered cell lines with tofacitinib or SH-4-54, IKZF1 wild-type cells were sensitive to each compound, suggesting JAK/STAT signaling plays a vital role in cell survival. In contrast, the IKZF1-deleted cells were relatively resistant to JAK/STAT inhibitors alone. However, in combination with dexamethasone, treatment of cells with sub-IC50 levels of SH-4-54 or tofacitinib resulted in re-sensitization to glucocorticoid-induced apoptosis. Conclusions: Our findings support that IKZF1 deletion leads to a targetable upregulation of the JAK/STAT pathway that, when inhibited, results in relative re-sensitization to dexamethasone. JAK/STAT pathway upregulation in IKZF1 deleted cells may be mediated by decreased expression of SOCS2. These results provide initial promise for targeting these vulnerabilities for the treatment of this poor-prognosis disease.

Integrative Analyses of mRNA Expression Profile Reveal SOCS2 and CISH Play Important Roles in GHR Mutation-Induced Excessive Abdominal Fat Deposition in the Sex-Linked Dwarf Chicken.

Sex-linked dwarf (SLD) chicken, which is caused by a recessive mutation of the growth hormone receptor (GHR), has been widely used in the Chinese broiler industry. However, it has been found that the SLD chicken has more abdominal fat deposition than normal chicken. Excessive fat deposition not only reduced the carcass quality of the broilers but also reduced the immunity of broilers to diseases. To find out the key genes and the precise regulatory pathways that were involved in the GHR mutation-induced excessive fat deposition, we used high-fat diet (HFD) and normal diet to feed the SLD chicken and normal chicken and analyzed the differentially expressed genes (DEGs) among the four groups. Results showed that the SLD chicken had more abdominal fat deposition and larger adipocytes size than normal chicken and HFD can promote abdominal fat deposition and induce adipocyte hypertrophy. RNA sequencing results of the livers and abdominal fats from the above chickens revealed that many DEGs between the SLD and normal chickens were enriched in fat metabolic pathways, such as peroxisome proliferator-activated receptor (PPAR) signaling, extracellular matrix (ECM)-receptor pathway, and fatty acid metabolism. Importantly, by constructing and analyzing the GHR-downstream regulatory network, we found that suppressor of cytokine signaling 2 (SOCS2) and cytokine-inducible SH2-containing protein (CISH) may involve in the GHR mutation-induced abdominal fat deposition in chicken. The ectopic expression of SOCS2 and CISH in liver-related cell line leghorn strain M chicken hepatoma (LMH) cell and immortalized chicken preadipocytes (ICP) revealed that these two genes can regulate fatty acid metabolism, adipocyte differentiation, and lipid droplet accumulation. Notably, overexpression of SOCS2 and CISH can rescue the hyperactive lipid metabolism and excessive lipid droplet accumulation of primary liver cell and preadipocytes that were isolated from the SLD chicken. This study found some genes and pathways involved in abdominal fat deposition of the SLD chicken and reveals that SOCS2 and CISH are two key genes involved in the GHR mutation-induced excessive fat deposition of the SLD chicken.

Ling-gui-zhu-gan decoction alleviates hepatic steatosis through SOCS2 modification by N6-methyladenosine

BackgroundThe ling-gui-zhu-gan (LGZG) decoction is a classic formula in traditional chinese medicine (TCM) and is widely used in clinical settings. Recently, the LGZG decoction was demonstrated to have an effect in alleviating hepatic steatosis induced by a high-fat diet (HFD). However, the mechanisms underlying this therapeutic effect remain unclear. The present study was designed to evaluate the effect and explore possible mechanisms of action of the LGZG decoction in nonalcoholic fatty liver disease (NAFLD). MethodsLiver tissue and blood samples were harvested. Liver steatosis, triglyceride (TG), liver total cholesterol (TC), liver low-density lipoprotein (LDL), serum almandine aminotransferase (ALT), aspartate aminotransferase (AST), and free fatty acid (FFA) were assayed. N6-methyladenosine (m6A) levels were estimated using an m6A RNA methylation quantification kit and immunohistochemistry. The m6A methylome was detected through methylated RNA immunoprecipitation sequencing (MeRIP-seq), followed by data analysis. The expression levels of differentially methylated genes (DMGs) were determined using real-time polymerase chain reaction and western blotting. ResultsThe LGZG decoction significantly alleviated hepatic steatosis and reduced m6A levels. MeRIP-seq revealed the coding sequence (CDS) domain to be the most critical modification site for m6A methylation, and the molecular functions of DMGs predominantly included insulin-like growth factor receptor binding and fatty acid metabolism and degradation. Further, LGZG treatment could reduce the m6A methylation levels of suppressor of cytokine signaling 2 (SOCS2), along with the expression of SOCS2 at mRNA and protein levels. ConclusionsThe LGZG decoction is an effective formula for treating NAFLD, and the possible mechanisms underlying its action could be related to N6-methyladenosine modification-medicated SOCS2.

Circ_0000526 Blocks the Progression of Breast Cancer by Sponging miR-492.

Aim: Breast cancer is one of the leading causes of cancer-associated death. This work aimed to explore the expression, function, and mechanism of circ_0000526 on the progression of breast cancer. Materials and Methods: The expressions of circ_0000526, miR-492, and suppressor of cytokine signaling 2 (SOCS2) in breast cancer samples were measured using quantitative real-time polymerase chain reaction. The correlation between pathological indexes of patients and the expression of circ_0000526 was also analyzed. Human breast cancer cell lines MCF-7 and MDA-MB-231 were applied to investigate the associated mechanism. Cell counting kit-8 assays were used to assess the effect of circ_0000526 on proliferation, and together with the wound healing assay, transwell assay was conducted to detect the effects of circ_0000526 on migration and invasion. Furthermore, luciferase reporter assay was used to verify the targeting relationship between miR-492 and circ_0000526. In addition, Western blot was performed to detect the regulatory effects of circ_0000526 on SOCS2. Results: Circ_0000526 expression in breast cancer samples was downregulated, which was correlated with unfavorable pathological indexes. It significantly inhibited the proliferation and metastasis of breast cancer cells, and facilitated apoptosis. The overexpression of circ_0000526 remarkably inhibited the expression of miR-492 by sponging it, and in turn promoted the expression of SOCS2. Conclusions: Circ_0000526 served as a tumor suppressor, which could function as the sponge of miR-492, an oncogenic microRNA, in breast cancer, and enhance the expression of tumor suppressor SOCS2 indirectly.

RETRACTED: Bone marrow mesenchymal stem cells-derived exosomal microRNA-185 represses ventricular remolding of mice with myocardial infarction by inhibiting SOCS2

Recently, the function of microRNAs (miRNAs) has been clarified in human diseases, we aimed to identify the role of miR-185 in myocardial infarction (MI). Bone marrow mesenchymal stem cells (BMSCs) were cultured, from which the exosomes were extracted. MI mice models were established by coronary artery ligation and injected with transfected BMSCs. The echocardiographic and ventricle indicators, and hemodynamics of mice were measured. Moreover, the ultrastructure and apoptosis of cardiomyocytes were determined, and expression of miR-185, suppressor of cytokine signaling 2 (SOCS2), collagens, and apoptotic proteins in myocardial tissues were evaluated. MiR-185 was poorly expressed in myocardial tissues of MI mice. BMSCs-Exo could shuttle miR-185 to promote cardiac function and attenuate myocardial injury of myocardial tissues in MI mice, and also could protect cardiomyocytes from apoptosis in MI mice by reducing the expression of SOCS2. SOCS2 was determined to be the direct target gene of miR-185. Overexpressed SOCS2 could block the cardioprotective effect of BMSCs-derived exosomal miR-185 in MI mice. We have found in this study that BMSCs-derived exosomal miR-185 could repress ventricular remolding of MI mice by inhibiting SOCS2. This study may provide new method for MI treatment.

SOCS2 affects the proliferation, migration and invasion of nasopharyngeal carcinoma cells via regulating EphA1.

Although the incidence of nasopharyngeal carcinoma (NPC) is relatively low, the mortality is very high and the patients have a poor prognosis. Thus, it is urgent to find a novel biomarker and a new therapeutic strategy. Suppressor of cytokine signaling-2 (SOCS2) was reported to be associated with various malignancies. However, the exact role of SOCS2 in NPC still remains largely unsure. In the present study, we showed that the expression of SOCS2 was significantly upregulated in NPC patients and cells. And the high expression of SOCS2 predicted a worse outcome in NPC patients. Moreover, the in vivo experiments indicated that knockout of SOCS2 inhibits the proliferation, migration, and invasion of NPC cells. Besides, we found a positive relationship between SOCS2 and EphA1 in NPC tissues. The rescue experiments indicated that SOCS2 affected the malignancy of NPC cells by regulating the expression of EphA1. Altogether, our data uncovered the ontogenetic role of SOCS2 dysregulation during the tumorigenesis of NPC. SOCS2 might serve as a biomarker during the diagnosis and treatment of NPC. And targeting SOCS2 might provide a novel treatment strategy for NPC patients.

MiR-875 can regulate the proliferation and apoptosis of non-small cell lung cancer cells via targeting SOCS2.

To investigate the effect of miR-875 on the proliferation and apoptosis of non-small cell lung cancer (NSCLC) cancer cell line A549 and the related mechanism. 30 paired tumor tissue and the adjacent tissue were collected. Real Time-quantitative Polymerase Chain Reaction (RT-qPCR) has been performed to detect the expression of miR-875 in NSCLC tissues and adjacent normal tissues. Moreover, suppressor of cytokine signaling 2 (SOCS2) has been predicted as a target of miR-875, and Dual-Luciferase reporter assay has been performed to confirm the targeting relationship; furthermore, the expression of SOCS2 in tumor tissue and the adjacent tissue were compared. Next, human NSCLC cell line A549 cells were cultured and transfected with miR-875 inhibitor with or without SOCS2 siRNA, and the proliferation and apoptosis of the cells were evaluated by Cell Counting Kit (CCK-8) and flow cytometry methods. Finally, the relative protein expression of Wnt and β-catenin were analyzed by Western blot analysis. MiR-875 was significantly up-regulated in NSCLC tissues compared with the adjacent tissues. SOCS2 was confirmed as a target of miR-875, and the expression of SOCS2 was markedly decreased in NSCLC tissues. Moreover, the knockdown of miR-875 inhibited the proliferation and promoted the apoptosis of A549 cells, while transfection of SOCS2 siRNA can block miR-875 inhibitor-induced anti-proliferative effects. Finally, the transfection of miR-875 inhibitor decreased the expression of Wnt and β-catenin, and SOCS2 siRNA can reverse the effect. MiR-875 may regulate the proliferation and apoptosis of NSCLC cells via targeting SOCS2, suggesting that miR-875 has the potential to become a therapeutic target for the treatment in NSCLC.

Suppressor of cytokine signaling 2 (SOCS2) negatively regulates the expression of antimicrobial peptides by affecting the Stat transcriptional activity in shrimp Marsupenaeus japonicus.

The suppressor of cytokine signaling (SOCS) family is a kind of negative regulators in the Janus kinase/signal transducer and activator of transcription (Jak/Stat) pathway in mammals and Drosophila. In kuruma shrimp, Marsupenaeus japonicus, SOCS2 is identified and its expression can be stimulated by peptidoglycan and polycytidylic acid. However, if SOCS2 participates in regulating Jak/Stat pathway in shrimp still needs further study. In this study, SOCS2 with Src homology 2 domain and SOCS box was identified in kuruma shrimp, M. japonicus. SOCS2 existed in hemocytes, heart, hepatopancreas, gills, stomach, and intestine, the expression of SOCS2 was upregulated significantly in the hemocytes and intestine of shrimp challenged with Vibrio anguillarum at 6h. To analyze SOCS2 function in shrimp immunity, bacterial clearance and survival rate were analyzed after knockdown of SOCS2 in shrimp challenged with V.anguillarum. Results showed that bacterial clearance increased, and the survival rate improved significantly comparing with controls. The SOCS2 was expressed in Escherichia coli and the recombinant SOCS2 was injected into shrimp, and Stat phosphorylation and translocation were analyzed. The result showed that "overexpression" of SOCS2 declined Stat phosphorylation level and inhibited Stat translocation into the nucleus. After knockdown of SOCS2 in shrimp prior to V.anguillarum infection, the expression level of antimicrobial peptides, including anti-lipopolysaccharide factors C1, C2 and D1, and Crustin I was upregulated significantly, and the expression of the AMPs was declined after recombinant SOCS2 injection. The SOCS2 expression was also decreased in Stat-knockdown shrimp challenged by V.anguillarum at 6 and 12h. Therefore, SOCS2 negatively regulates the AMP expression by inhibiting Stat phosphorylation and translocation into nucleus in shrimp, meanwhile, SOCS2 expression was also regulated by Jak/Stat pathway.

A novel role of suppressor of cytokine signaling-2 in the regulation of TrkA neurotrophin receptor biology

Suppressor of cytokine signaling-2 (SOCS2) is a regulator of intracellular responses to growth factors and cytokines. Cultured dorsal root ganglia neurons from neonatal mice with increased or decreased SOCS2 expression were examined for altered responsiveness to nerve growth factor (NGF). In the presence of NGF, SOCS2 over-expression increased neurite length and complexity, whereas loss of SOCS2 reduced neurite outgrowth. Neither loss nor gain of SOCS2 expression altered the relative survival of these cells, suggesting that SOCS2 can discriminate between the differentiation and survival responses to NGF. Interaction studies in 293T cells revealed that SOCS2 immunoprecipitates with TrkA and a juxtamembrane motif of TrkA was required for this interaction. SOCS2 also immunoprecipitated with endogenous TrkA in PC12 Tet-On cells. Over-expression of SOCS2 in PC12 Tet-On cells increased total and surface TrkA expression. In contrast, dorsal root ganglion neurons which over-expressed SOCS2 did not exhibit significant changes in total levels but an increase in surface TrkA was noted. SOCS2-induced neurite outgrowth in PC12 Tet-On cells correlated with increased and prolonged activation of pAKT and pErk1/2 and required an intact SOCS2 SH2 domain and SOCS box domain. This study highlights a novel role for SOCS2 in the regulation of TrkA signaling and biology.

Expression and significance of suppressor of cytokine signaling 2 and signal transducers and activators of transcription 5 in hepatocellular carcinoma

Objective To investigate the expression of suppressor of cytokine signaling 2 (SOCS2) and signal transducers and activators of transcription 5 (STAT5) in hepatocellular carcinoma (HCC) and their correlation to clinicopathologial features.Methods The mRNA and protein expression levels of SOCS2 and STAT5 in 84 cases of HCC and corresponding paracarninoma tissues were detected by using reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohisochemistry (IHC),respectively.The semiquantitative analysis results and clinical data were statistically analyzed.Results The expression of SOCS2 mRNA in hepatoma tissue and adjacent hepatic tissue to carcinoma respectively was 0.089 ± 0.034 and 0.340 ± 0.083 (P ＜ 0.05).The expression of STAT5 mRNA in hepatoma tissue and adjacent hepatic tissue to carcinoma respectively was 0.532 ± 0.094 and 0.276 ± 0.065 (P ＜ 0.05).The expression of SOCS2 was lower in hepatoma tissue,and that of STAT5 was higher in hepatoma.There was a negative correlation between them in HCC.(r =-0.612,P ＜ 0.01 for mRNA ; r =-0.574,P ＜ 0.01 for protein,respectively).Conclusion There is low expression of SOCS2,and overexpression of STAT5 in HCC.SOCS2 and STAT5 both or alone may participate in the occurrence and development of HCC. Key words: Carcinoma, hepatocellular; Suppressor of cytokine signaling 2 ; Signal transducers and activators of transcription 5

Effect of suppressor of cytokine signaling 2 (SOCS2) on fat metabolism induced by growth hormone (GH) in porcine primary adipocyte

SOCS2, a member of suppressor of cytokine signaling (SOCS) family, is a negative regulator of the signal pathway Janus kinase/signal transducers and activators of transcription (JAK/STAT). Growth hormone (GH) could stimulate lipolysis in adipose tissue. To demonstrate the specific influence of SOCS2 on porcine adipocytes differentiation and lipid metabolism induced by GH, we induced porcine primary adipocytes with 500 ng/ml GH and then tested the triglyceride (TG) accumulation and mRNA expressions of crucial genes in lipid metabolism like peroxisome proliferator-activated receptor gamma (PPARγ), fatty acid synthase (FAS), adipose triglyceride lipase (ATGL), hormone-sensitive lipase (HSL), SOCS2 and SOCS3. Then we retested these genes expressions in different time point after further treatment that over expressed SOCS2 in primary adipocytes and treated with 500 ng/ml GH. Results showed 500 ng/ml GH significantly restrained the porcine primary adipocytes differentiation. Specifically, 0.5 h after the induction with GH, accumulation of TG began to increase, and turned down since 8 h after. GH could promote PPARγ and FAS expressions during earlier stage (0-1 h), restrain from 4 h. However, ATGL and HSL mRNA expressions were stabile increasing. The expression of SOCS2 increased steadily after GH stimulation while SOCS3 expression was instantaneous rise. Overexpression of SOCS2 significantly decreased GH-induced the increase of PPARγ, FAS, ATGL and HSL mRNA expressions in earlier stage (0-1 h), as well as FAS and ATGL protein expression. Otherwise SOCS2 overexpression significantly decreased signal transducers and activators of transcription 3 (STAT3), signal transducers and activators of transcription 5 (STAT5) mRNA expressions and tyrosine phosphorylation levels with GH stimulation. At the same time SOCS3 mRNA kept in a lower level in Ad-SOCS2 transfected adipocytes. In conclusion, SOCS2 might be an important negative regulator of GH signaling in porcine adipocytes, which would provide the ground work for the mechanism of SOCS2 regulation fat metabolism.

Effect of acupuncture-moxibustion on the expression of IGF-1 and SOCS2 in colonic mucosa of rats with ulcerative colitis

Objective: To observe the effect of acupuncture-moxibustion on the expression of insulin-like growth factor-1 (IGF-1) and suppressor of cytokine signaling-2 (SOCS2) in colonic mucosa of rat models of ulcerative colitis (UC), and explore the mechanism of acupuncture- moxibustion therapy in treating UC. Methods: The rats were randomized into a normal control (NC) group, a model control (MC) group, an herb-partitioned moxibustion (HPM) group and an electroacupuncture (EA) group, 8 in each group. The rat models of UC were established by immunological methods combined with local stimulation. The rats in the HPM and EA groups were given herb-partitioned moxibustion and electroacupuncture treatments respectively, once every day, lasting for 14 d. The morphological variations of rat's colonic mucosa were observed under light microscope; the colonic mucosal mucin was detected by PAS-AB and HID-AB staining methods; the expression of IGF-1 and SOCS2 was assayed by the immunohistochemical method. Results: In the rat models of UC, ulceration and inflammation of the colon were revealed by light microscope. The concentration of colonic mucosal mucin was reduced (P<0.01), while the expression of IGF-1 had an increase (P<0.01), and the expression of SOCS2 was reduced (P<0.01). After HPM or EA treatment, the pathological injuries of colonic mucosa had improved, the concentration of mucin increased (P<0.01), the expression of IGF-1 decreased (P<0.01), and the expression of SOCS2 increased (P<0.01). Conclusion: The secretion of mucosal mucin in rat UC decreased, the expression of IGF-1 was significantly higher, while the expression of SOCS2 was remarkably lower; both HPM and EA can help improve the damage of colonic mucosa in rat UC, and modulate the secretion of mucin, as well as regulate the expression of IGF-1 and SOCS2 in the colonic mucosa.

Enhanced Expression of SOCS-2 in the Rat Hippocampus after Transient Forebrain Ischemia

Suppressor of cytokine signaling-2 (SOCS-2) has recently been identified as an important regulator involved in neuronal differentiation and maturation. However, the role of SOCS-2 in ischemia-induced hippocampal neurogenesis remains to be clarified. Here we investigated the spatiotemporal expression of SOCS-2 in the rat hippocampus following transient forebrain ischemia, and particular attention was paid to changes in the dentate gyrus. SOCS-2 mRNA was constitutively expressed in hippocampal neurons and astrocytes in control animals. However, its upregulation occurred specifically in reactive astrocytes in the hippocampus proper, in particular the CA1 and dentate hilar regions, at day 3 after reperfusion, and was sustained for more than 2 weeks. In addition to the CA1 and hilar regions, SOCS-2 was transiently increased in the subgranular zone (SGZ) of the dentate gyrus on days 3-7 after reperfusion. This correlated with the post-ischemic upregulation of SOCS-2 in the CA1 or dentate gyrus subfield, including the SGZ detected by semiquantitative reverse transcriptase-polymerase chain reaction analysis. The majority of the SOCS-2-expressing cells in the SGZ were co-labeled with glial fibrillary acidic protein (GFAP), and a subpopulation of GFAP/SOCS-2 double-labeled cells in the SGZ co-expressed the neural progenitor marker nestin, or the proliferation marker proliferating cellular nuclear antigen. In addition, a subset of SOCS-2-labeled cells in the SGZ expressed the immature neuronal marker polysialic acid-neural cell adhesion molecule. These data suggest that SOCS-2 may be involved in glial reactions, and possibly adult hippocampal neurogenesis during ischemic insults.

Reduced expression of TAC1, PENK and SOCS2 in Hcrtr-2 mutated narcoleptic dog brain

BackgroundNarcolepsy causes dramatic behavioral alterations in both humans and dogs, with excessive sleepiness and cataplexy triggered by emotional stimuli. Deficiencies in the hypocretin system are well established as the origin of the condition; both from studies in humans who lack the hypocretin ligand (HCRT) and in dogs with a mutation in hypocretin receptor 2 (HCRTR2). However, little is known about molecular alterations downstream of the hypocretin signals.ResultsBy using microarray technology we have screened the expression of 29760 genes in the brains of Doberman dogs with a heritable form of narcolepsy (homozygous for the canarc-1 [HCRTR-2-2] mutation), and their unaffected heterozygous siblings. We identified two neuropeptide precursor molecules, Tachykinin precursor 1 (TAC1) and Proenkephalin (PENK), that together with Suppressor of cytokine signaling 2 (SOCS2), showed reduced expression in narcoleptic brains. The difference was particularly pronounced in the amygdala, where mRNA levels of PENK were 6.2 fold lower in narcoleptic dogs than in heterozygous siblings, and TAC1 and SOCS2 showed 4.4 fold and 2.8 fold decrease in expression, respectively. The results obtained from microarray experiments were confirmed by real-time RT-PCR. Interestingly, it was previously shown that a single dose of amphetamine-like stimulants able to increase wakefulness in the dogs, also produce an increase in the expression of both TAC1 and PENK in mice.ConclusionThese results suggest that TAC1, PENK and SOCS2 might be intimately connected with the excessive daytime sleepiness not only in dogs, but also in other species, possibly including humans.

Erythropoietin up-regulates SOCS2 in neuronal progenitor cells derived from SVZ of adult rat.

We examined the effects of EPO on expression of suppressor of cytokine signaling 2 (SOCS2) and found that treatment of neural progenitor cells derived from the adult subventricular zone (SVZ) with recombinant human EPO (rhEPO) stimulated progenitor cell differentiation into neurons, but not astrocytes. Quantitative RT-PCR revealed that SOCS2 mRNA levels were increased in the progenitor cells treated with rhEPO. Immunostaining showed that neurons but not astrocytes were SOCS2 immunoreactive. Incubation of the progenitor cells with rhEPO in the presence of a neutralizing antibody against EPO abolished the effects of EPO on neuronal differentiation and expression of SOCS2. Our data suggest that up-regulation of SOCS2 in neuronal progenitor cells derived from the adult SVZ may regulate EPO enhanced neuronal differentiation.