1.Growth Differentiation Factor 15 Inhibits Elevated Expression of Matrix Metalloproteinase 1 Induced by Pooled Serum in Patients with Coroanry Artery Ectasia.
Rui-feng LIU ; Wei WU ; Lian-feng CHEN ; Xue-qing ZHU ; Shu-yang ZHANG
Acta Academiae Medicinae Sinicae 2015;37(5):520-527
OBJECTIVETo observe the effects of coroanry artery ectasia (CAE) patients' pooled serum on the main proteinases and extracellular matrix (ECM) synthesis and explore whether the growth differentiation factor 15(GDF 15) can regulate the characteristic changes induced by CAE patients' pooled serum.
METHODSSerum samples were collected from 32 CAE patients, 30 patients with coronary heart disease (CHD), and 31 subjects with normal coronary arteries (CON) and then mixed in the same volumes by groups. Then human umbilical vein smooth muscle cells were cultured with the media containing 25% pooled serum. After having been disposed, proteinase system and ECM synthesis system were detected in the cell and culture media samples. GDF15 or GDF15 antibodies was added into the 25% pooled serum in each group to observe if GDF 15 could impact the characteristic changes induced by CAE patients' pooled serum.
RESULTSThe expression of matrix metalloproteinases (MMP) 1 mRNA in CAE group was significantly higher than CON group (P=0.002) and CHD group (P=0.000), the secretory MMP1 protein and total MMPs activity in culture media were also upregulated in CAE group (both P<0.01). After adding GDF 15 into the culture media (GDF15+CAE group), the MMP1 mRNA ,secretory MMP1 protein, and total MMPs activity were significantly lower than CAE group (all P<0.01), while in the GDF15 antibody+CAE group, the MMP1 mRNA and total MMPs activities were significantly higher than in GDF15+CAE group (both P<0.01), but the secretory MMP1 protein was not different from GDF 15+CAE group (P>0.05).
CONCLUSIONThe vascular smooth muscle cells may participate in the CAE process mainly by regulating MMPs system but not the elastase 2 or ECM synthesis system, and GDF15 may be an compensatory factor to prohibit the over-destruction of coronary ECM induced by MMPs.
Biomarkers ; blood ; Coronary Artery Disease ; Dilatation, Pathologic ; Growth Differentiation Factor 15 ; Humans ; Matrix Metalloproteinase 1
2.Analysis of differential expression genes related to different metastasis potential of adenoid cystic carcinoma using restriction fragments differential display PCR.
You-guang LU ; Hong-ying ZHOU ; Lin-can DING ; Yan MEI ; Ruo-hong XIONG ; Shi-shan DENG ; Hui-jun YANG
Chinese Journal of Medical Genetics 2006;23(5):505-510
OBJECTIVETo construct differential expression profiles of adenoid cystic carcinoma cell lines for screening candidate genes related to metastasis and to verify some candidate genes in adenoid cystic carcinoma.
METHODSRestriction fragments differential display PCR (RFDD-PCR) was used to set up gene expression profiles of adenoid cystic carcinoma cell lines-ACC-M and ACC-2, with high and low metastasis potential respectively. Candidate genes were screened through bioinformatics analysis. Then, a gene family of these candidate genes was checked using semi-quantitative reverse transcription-PCR(RT-PCR).
RESULTSTwo gene expression profiles including 5420 gene fragments were constructed, 12 genes of a family called matrix metalloproteinase genes (MMPs) were observed obvious differentially expressed between two cell lines. Results of semi-quantitative RT-PCR also identified this different expression of MMP2,MMP7,MMP9,MMP14,MMP15 and MMP24.
CONCLUSIONThe construction of gene expression profiles of ACC-M and ACC-2 cell lines makes the foundation for seeking the target genes of adenoid cystic carcinoma. MMP2,MMP7,MMP9 and MMP15 may be relevant with carcinogenesis, development and metastasis of adenoid cystic carcinoma, and different metastasis potential may result from different subtype of MMPs gene family.
Carcinoma, Adenoid Cystic ; enzymology ; genetics ; pathology ; Cell Line, Tumor ; Gene Expression Profiling ; Gene Expression Regulation, Enzymologic ; Gene Expression Regulation, Neoplastic ; Humans ; Matrix Metalloproteinase 15 ; genetics ; Matrix Metalloproteinase 2 ; genetics ; Matrix Metalloproteinase 7 ; genetics ; Matrix Metalloproteinase 9 ; genetics ; Matrix Metalloproteinases ; genetics ; Neoplasm Metastasis ; Reverse Transcriptase Polymerase Chain Reaction ; methods