• Title/Summary/Keyword: downregulation

검색결과 535건 처리시간 0.03초

Expression of HBP2 in Human Spermatogonial Stem Cell-like Cells from Nonobstructive Azoospermia Patients and Its Role in G1/S Transition & Downregulation in Colon Cancer

  • Yoo, Jung-Ki;Lee, Dong-Ryul;Lim, Jung-Jin;Kim, Jin-Kyeoung
    • Reproductive and Developmental Biology
    • /
    • 제32권4호
    • /
    • pp.211-215
    • /
    • 2008
  • The HMG box containing protein (HBP) has a high mobility group domain and involved in the regulation of proliferation and differentiation of tissues. We screened HBP2 in glioblastoma using Suppression Subtractive Hybridization (SSH) and isolated human spermatogonial stem cell-like cells (hSSC-like cells) derived from patients of nonobstructive azoospermia (NOA). Expression of HBP2 was analyzed by RT-PCR in undifferentiated stem cells (human Embryonic Stem Cells, hSSC-like cells 2P) and spontaneous differentiated stem cells (hSSC-like cells 4P). It was overexpressed in hESC and hSSC-like cells 2P but not in hSSC-like cells 4P. Also, the expression level of HBP2 was downregulated in colon tumor tissues compared to normal tissues. Specifically in synchronized WI-38 cells, HBP2 was highly upregulated until the G1 phase of the cell cycle and gradually decreased during the S phase. Our results suggest that HBP2 was downregulated during the spontaneous differentiation of hSSC-like cells. HBP2 was differently expressed in colon tissues and was related to G1-progression in WI-38 cells. It may playa role in the maintenance of an undifferentiated hSSC-like cell state and transits from G1 to S in WI-38 cells. This research was important that it identified a biomarker for an undifferentiated state of hSSC-like cells and characterized its involvement to arrest during cell cycle in colon cancer.

면역독성학적 분석에 의한 축산업 종사자들의 건강 유해성 평가 (Immunologic Alteration Demonstrated at the Economic Animal Husbandry Workers)

  • 김형아;이경숙;김경란;김광호;허용
    • Toxicological Research
    • /
    • 제21권2호
    • /
    • pp.121-128
    • /
    • 2005
  • Economic animal husbandry workers exposed to organic dust can be suffered from immunologic disorders. Our study was to determine immunological parameters related with occurrence of respiratory allergic diseases to animal husbandry workers in Korea for the first time. Peripheral blood were obtained from twenty-five pig barn workers, forty-nine chicken farming workers and fifty-one non-agricultural control workers. Significantly upregulated plasma IgE level was observed with pig-barn workers than that of chicken farming workers or healthy community control subjects. Furthermore, level of histamine, a hallmark of allergy induction, was upregulated in the pig and chicken farming workers in comparison with that of the control subjects. Downregulation of $IFN_\gamma$ and $TNF_{\alpha}$ production from T cells was apparent in the animal husbandry workers compared with the control subjects. Meanwhile, T cells collected from the pig barn workers demonstrated significantly higher production of IL-4 and IL-10 than the other groups. There were also alterations in IgG subclass distribution. In conclusion, immunological modulation probably leading to occupational allergic diseases can be occurred in the economic animal husbandry workers and the pig barn workers could be the most risky group to the work-related allergic disease.

3T3-L1 전지방세포에서 연잎-연근 혼합 발효물의 지방세포 분화 억제 효과 (Effects of Fermented Lotus Extracts on the Differentiation in 3T3-L1 Preadipocytes)

  • 이신지;;이수진;정지은;구병수;김동일;김호준
    • 한방비만학회지
    • /
    • 제13권2호
    • /
    • pp.74-83
    • /
    • 2013
  • Objectives: This study was performed to evaluate the effects of fermented lotus extracts on the inhibition of differentiation in 3T3-L1 preadipocytes. Methods: Extracts of lotus leaf and lotus root were fermented using 4 different probiotics separately, including Lactobacillus plantarum, Lactobacillus rhamnosus, Bifidobacterium breve, and Bifidobacterium longum. Inhibition of preadipocyte differentiation was examined by Oil red O dye staining. Expressions of adipogenic transcription factors including CCAAT/enhancer binding proteins (C/$EBP{\alpha}$) and peroxisome proliferators-activated receptor ${\gamma}$ ($PPAR{\gamma}$) were analyzed by real time polymerase chain reaction and Western blotting analysis. Results: Fermented lotus extracts inhibited adipogenic transcription factors by inhibiting preadipocytes differentiation. All of the groups fermented by 4 kinds of probiotics showed reduction in Oil Red O dye staining. Bifidobacterium breve showed the most effective inhibition of C/$EBP{\alpha}$. Bifidobacterium breve and Bifidobacterium longum showed the best downregulation of $PPAR{\gamma}$ expressions compared with the control and the unfermented lotus group. Conclusions: Fermented lotus extracts showed significant effects on inhibition of preadipocyte differentiation in 3T3-L1 preadipocytes showing correlation with insulin sensitivity and lipid metabolism related with obesity.

Tiul1 and TGIF are Involved in Downregulation of $TGF{\beta}1$-induced IgA Isotype Expression

  • Park, Kyoung-Hoon;Nam, Eun-Hee;Seo, Goo-Young;Seo, Su-Ryeon;Kim, Pyeung-Hyeun
    • IMMUNE NETWORK
    • /
    • 제9권6호
    • /
    • pp.248-254
    • /
    • 2009
  • [ $TGF-{\beta}1$ ]is well known to induce Ig germ-line ${\alpha}$ ($GL{\alpha}$) transcription and subsequent IgA isotype class switching recombination (CSR). Homeodomain protein TG-interacting factor (TGIF) and E3-ubiquitin ligases TGIF interacting ubiquitin ligase 1 (Tiul1) are implicated in the negative regulation of $TGF-{\beta}$ signaling. In the present study, we investigated the roles of Tiul1 and TGIF in $TGF{\beta}1$-induced IgA CSR. We found that over-expression of Tiul1 decreased $TGF{\beta}1$-induced $GL{\alpha}$ promoter activity and strengthened the inhibitory effect of Smad7 on the promoter activity. Likewise, overexpression of TGIF also diminished $GL{\alpha}$ promoter activity and further strengthened the inhibitory effect of Tiul1, suggesting that Tiul1 and TGIF can down-regulate $TGF{\beta}1$-induced $GL{\alpha}$ expression. In parallel, overexpression of Tiul1 decreased the expression of endogenous IgA CSR-predicitive transcripts ($GLT_{\alpha},\;PST_{\alpha},\;and\;CT_{\alpha}$) and $TGF{\beta}1$-induced IgA secretion, but not $GLT_{\gamma3}$ and IgG3 secretion. Here, over-expressed TGIF further strengthened the inhibitory effect of Tiul1. These results suggest that Tiul1 and TGIF act as negatively regulators in $TGF{\beta}1$-induced IgA isotype expression.

봉독약침액(蜂毒藥鍼液)이 비만세포주의 CD/cytokine 유전자(遺傳子) 발현(發現)에 미치는 영향(影響) (Microarray Analysis of CD/cytokine Gene Expression in Human Mast Cell treated with Bee Venom)

  • 이웅경;강성길;고형균
    • Journal of Acupuncture Research
    • /
    • 제20권5호
    • /
    • pp.50-62
    • /
    • 2003
  • Objective: Bee Venom(BV) has been used for various kinds of inflammatory or painful conditions in Oriental Medicine clinics, and there publishes reports on its therapeutic effects and the probable mechanism of those therapeutic effects, where CDs and cytokines plays important role. This study investigated the influences of bee venom on the expressions of CDs and cytokines of HMC cell line Methods: In this study we analysed the expression profile of HMC cell line treated with BV of 10-2ug/ml in relation to that of HMC cell line treated with vehicle by way of CD/cytokine microarray hybridization with 342 genes on it. Results: There were no upregulated genes by more than 3 fold, while there showed some downregulated genes by less than 1/3 fold as follows: colony stimulating factor 2, CD122, IL-7, CD112, TNF-alpha, CD138, CD166, TGFbetaR2, CD42b, CD62L, CD111, interleukin 10 receptor alpha, colony stimulating factor 1(macrophage), CD38 antigen(p45), CD121a, CD33 antigen(gp67), colony stimulating factor 1 receptor, B cell linker protein (SLP65) mRNA, CD94, alanyl(membrane) aminopeptidase, immunoglobulin(CD79A) binding protein 1, CD205, CD241, CD207, CDw121b, integrin alpha L(CD11a), integrin beta 1(CD29), CD91, CD42b. Conclusions: Bee venom treatment induced downregulation of some CDs or cytokines including $TNF-{\alpha}$. IL-1R with its possible implication in an antiinflammatory action of BV. Further research on expression profile changes induced by BV treatment is expected.

  • PDF

Intragenic DNA Methylation Concomitant with Repression of ATP4B and ATP4A Gene Expression in Gastric Cancer is a Potential Serum Biomarker

  • Raja, Uthandaraman Mahalinga;Gopal, Gopisetty;Rajkumar, Thangarajan
    • Asian Pacific Journal of Cancer Prevention
    • /
    • 제13권11호
    • /
    • pp.5563-5568
    • /
    • 2012
  • Based on our previous report on gastric cancer which documented ATP4A and ATP4B mRNA down-regulation in gastric tumors relative to normal gastric tissues, we hypothesized that epigenetic mechanisms could be responsible. ATP4A and ATP4B mRNA expression in gastric cancer cell lines AGS, SNU638 and NUGC-3 was examined using reverse transcriptase PCR (RT-PCR). AGS cells were treated with TSA or 5'-AzaDC and methylation specific PCR (MSP) and bisulfite sequencing PCR (BSP) analysis were performed. MSP analysis was on DNA from paraffin embedded tissues sections and plasma. Expression analysis revealed downregulation of ATP4A and ATP4B genes in gastric cancer cell lines relative to normal gastric tissue, while treatment with 5'-AzaDC re-activated expression of both. Search for CpG islands in their putative promoter regions did not indicate CpG islands (CGI) but only further downstream in the bodies of the genes. Methylation specific PCR (MSP) in the exon1 of the ATP4B gene and exon7 in ATP4A indicated methylation in all the gastric cancer cell lines tested. MSP analysis in tumor tissue samples revealed methylation in the majority of tumor samples, 15/19, for ATP4B and 8/8 for ATP4A. There was concordance between ATP4B and ATP4A down-regulation and methylation status in the tumour samples tested. ATP4B methylation was detectable in cell free DNA from gastric cancer patient's plasma samples. Thus ATP4A and ATP4B down-regulation involves DNA methylation and methylated ATP4B DNA in plasma is a potential biomarker for gastric cancer.

shRNA Mediated RHOXF1 Silencing Influences Expression of BCL2 but not CASP8 in MCF-7 and MDA-MB-231 Cell Lines

  • Ghafouri-Fard, Soudeh;Abdollahi, Davood Zare;Omrani, Mirdavood;Azizi, Faezeh
    • Asian Pacific Journal of Cancer Prevention
    • /
    • 제13권11호
    • /
    • pp.5865-5869
    • /
    • 2012
  • RHOXF1 has been shown to be expressed in embryonic stem cells, adult germline stem cells and some cancer lines. It has been proposed as a candidate gene to encode transcription factors regulating downstream genes in the human testis with antiapoptotic effects. Its expression in cancer cell lines has implied a similar role in the process of tumorigenesis. The human breast cancer cell lines MDA-MB-231 and MCF-7 were cultured in DMEM medium and transfected with a pGFP-V-RS plasmid bearing an RHOXF1 specific shRNA. Quantitative real-time RT-PCR was performed for RHOXF1, CASP8, BCL2 and HPRT genes. Decreased RHOXF1 expression was confirmed in cells after transfection. shRNA knock down of RHOXF1 resulted in significantly decreased BCL2 expression in both cell lines but no change in CASP8 expression. shRNA targeting RHOXF1 was shown to specifically mediate RHOXF1 gene silencing, so RHOXF1 can mediate transcriptional activation of the BCL2 in cancers and may render tumor cells resistant to apoptotic cell death induced by anticancer therapy. shRNA mediated knock down of RHOXF1 can be effective in induction of apoptotic pathway in cancer cells via BCL2 downregulation, so it can have potential therapeutic utility for human breast cancer.

Sensitization of Cervical Carcinoma Cells to Paclitaxel by an IPP5 Active Mutant

  • Zeng, Qi-Yan;Huang, Yu;Zeng, Lin-Jie;Huang, Min;Huang, Yong-Qi;Zhu, Qi-Fang
    • Asian Pacific Journal of Cancer Prevention
    • /
    • 제15권19호
    • /
    • pp.8337-8343
    • /
    • 2014
  • Paclitaxel is one of the best anticancer agents that has been isolated from plants, but its major disadvantage is its dose-limiting toxicity. In this study, we obtained evidence that the active mutant IPP5 ($8-60hIPP5^m$), the latest member of the inhibitory molecules for protein phosphatase 1, sensitizes human cervix carcinoma cells HeLa more efficiently to the therapeutic effects of paclitaxel. The combination of $8-60hIPP5^m$ with paclitaxel augmented anticancer effects as compared to paclitaxel alone as evidenced by reduced DNA synthesis and increased cytotoxicity in HeLa cells. Furthermore, our results revealed that $8-60hIPP5^m$ enhances paclitaxel-induced G2/M arrest and apoptosis, and augments paclitaxel-induced activation of caspases and release of cytochrome C. Evaluation of signaling pathways indicated that this synergism was in part related to downregulation of NF-${\kappa}B$ activation and serine/threonine kinase Akt pathways. We noted that $8-60hIPP5^m$ downregulated the paclitaxel-induced NF-${\kappa}B$ activation, $I{\kappa}B{\alpha}$ degradation, PI3-K activity and phosphorylation of the serine/threonine kinase Akt, a survival signal which in many instances is regulated by NF-${\kappa}B$. Together, our observations indicate that paclitaxel in combination with $8-60hIPP5^m$ may provide a therapeutic advantage for the treatment of human cervical carcinoma.

Bag-1L is a Stress-withstand Molecule Prevents the Downregulation of Mcl-1 and c-Raf Under Control of Heat Shock Proteins in Cisplatin Treated HeLa Cervix Cancer Cells

  • Ozfiliz, Pelin;Arisan, Elif Damla;Coker-Gurkan, Ajda;Obakan, Pinar;Eralp, Tugce Nur;Dinler-Doganay, Gizem;Palavan-Unsal, Narcin
    • Asian Pacific Journal of Cancer Prevention
    • /
    • 제15권11호
    • /
    • pp.4475-4482
    • /
    • 2014
  • Background: Cisplatin, a DNA damaging agent, induces apoptosis through increasing DNA fragmentation. However, identification of intrinsic resistance molecules against Cisplatin is vital to estimate the success of therapy. Bag-1 (Bcl-2-associated anthanogene) is one anti-apoptotic protein involved in drug resistance impacting on therapeutic efficiency. Elevated levels of this protein are related with increase cell proliferation rates, motility and also cancer development. For this reason, we aimed to understand the role of Bag-1 expression in Cisplatin-induced apoptosis in HeLa cervix cancer cells. Cisplatin decreased cell viability in time- and dose-dependent manner in wt and Bag-1L+HeLa cells. Although, $10{\mu}M$ Cisplatin treatment induced cell death within 24h by activating caspases in wt cells, Bag-1L stable transfection protected cells against Cisplatin treatment. To assess the potential protective role of Bag-1, we first checked the expression profile of interacting anti-apoptotic partners of Bag-1. We found that forced Bag-1L expression prevented Cisplatin-induced apoptosis through acting on Mcl-1 expression, which was reduced after Cisplatin treatment in wt HeLa cells. This mechanism was also supported by the regulation of heat shock protein (Hsp) family members, Hsp90 and Hsp40, which were involved in the regulation Bag-1 interactome including several anti-apoptotic Bcl-2 family members and c-Raf.

Baicalein Treatment Promotes Osteoblast Proliferation and Osteogenic Differentiation through Activation of Immediate Early Response 3

  • Lee, Sang-Im
    • 치위생과학회지
    • /
    • 제19권4호
    • /
    • pp.254-260
    • /
    • 2019
  • Background: The primary aims of periodontal disease treatment is to remove dental plaque and calculus, the main causes of tooth loss, and restore periodontal tissue destroyed by inflammation. Periodontal disease treatment should also help maintain the alveolar bone, alleviate inflammation, and promote periodontal ligament cell proliferation, which is essential for tissue regeneration. Conventional antibiotics and anti-inflammatories have adverse side effects, especially during long-term use, so there is a need for adjunct treatment agents derived from natural products. The purpose of this study was to investigate whether the herbal flavone baicalein has the osteogenic activity under inflammatory conditions, and assess the involvement of osteoblast immediate early response 3 (IER3) expression. Methods: Human osteoblastic MG-63 cells were cultured with the pro-inflammatory cytokines tumor necrosis factor α and interleukin 1β in the presence and absence of baicalein. Proliferation was assessed using the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay, and expression of IER3 mRNA was assessed using real-time polymerase chain reaction. The expression of IER3 protein levels and activation of associated signal transduction pathways were assessed using western blotting. Results: Baicalein increased IER3 mRNA and protein expression synergistically. In addition, baicalein reversed the suppression of cell proliferation, and the downregulation of osteogenic transcription factor runt-related transcription factor 2 and osterix induced by pro-inflammatory cytokines. Baicalein also upregulated the phosphorylation of c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK 1/2). The upregulation of IER3 by pro-inflammatory cytokines was blocked by pretreatment with inhibitors of AKT, p38, JNK, and ERK 1/2. Conclusion: Baicalein mitigates the deleterious responses of osteoblasts to pro-inflammatory cytokines. Further, IER3 enhanced the effect of baicalein via activation of AKT, p38, JNK, and ERK pathways.