Dynamic changes in type Ⅰ collagen, MMP- 1 and TIMP- 1 after angioplasty

Objective To investigate the dynamic changes of type Ⅰ collagen, and the activity of meta lloproteinases- 1 (MMP- 1) and tissue inhibitor of metalloproteinases- 1 (TIMP- 1) after angioplasty. Methods The restenotic model of iliac arteries of domestic microswine was established wi th hypercholesterol feed plus two angioplasties. Angioplastied vessels were har vested at the end of 1, 2, 3 and 6 months after the second angioplasty. Immunoh istochemistry, transmission electronic microscopy and image quantitative analys is techniques were employed to study neointimal proliferation, the phenotype of vascular smooth muscle cells (VSMC) and the expression of type Ⅰ collagen, MMP - 1 and TIMP- 1. Results The peak of vascular neointimal proliferation was at 3 months after angioplasty . The expression of type Ⅰ collagen gradually increased from 1 to 6 months aft er angioplasty. For MMP- 1, expression was lower in the early stage after angio plasty but increase to normal levels of control vessels at 6 months after angiop lasty. Expression of TIMP- 1 rapidly increased in the early phase after angiopl asty, reached peak at 3 months and maintained the high level till 6 months after angioplasty. Meanwhile, the VSMC was predominantly the synthetic phenotype at the early stage and was transformed to the contractive phenotype at the late sta ge after angioplasty. The ratio of TIMP- 1 and MMP- 1 was positively related to the area of the neointima and the expression of type Ⅰ collagen respectively (P<0. 01). Conclusion Type Ⅰ collagen increased gradually after angioplasty, which might be determine d by the ratio of TIMP- 1/MMP- 1 and also related to the phenotype of VSMC.     

Relationship between expression of type Ⅲ collagen and phenotype of vascular smooth muscle cells in neointimal of stented coronary artery

Objective To investigate the secretive features of type Ⅲ collagen in restenosis of the stented coronary artery and the relationship between the expression of type Ⅲ collagen and vascular smooth muscle cells (VSMCs). Methods An animal model of restenosis was established by implanting oversized tantalum stents into the coronary arteries in 26 dogs. At the 7th, 14th and 28th days after implantation, the stented coronaries were harvested. Transmission electronic microscopy and immunohistochemistry were employed to investigate the features of type Ⅲ collagen secretion and VSMCs’ phenotype. The expression of type Ⅲ collagen was quantified and compared for the three stages. Results Migration and proliferation of VSMCs were the main features at the 7th day after injury. At the 14th day, proliferation of VSMCs reached the peak while much more secretion of collagen was noticeable. VSMCs began to transform from the synthetic phenotype to the contractile phenotype at the 28th day, when a great quantity of collagen was also secreted. The quantity of secreted type Ⅲ collagen was greater at the 14th and 28th day than that at the 7th day (P<0.05). The stain density of type Ⅲ collagen was positively correlated to neointimal thickness at both of 14th and 28th day. Conclusion The pathological bases of restenosis are variant in different period of restenosis formation. Type Ⅲ collagen may play an important role in the late stage of restenosis after coronary stenting.     

Significance of elevated serum concentration of type Ⅰ collagen metabolites and its correlation with serum interleukin 6 activities in multiple myeloma

Bonelyticlesionsandsystematicosteoporosisarecharacteristicclinicalmanifestationsinmultiplemyeloma(MM),whichseverelythreatenthesurvivalquantityofthepatients.RecentstudieslljhaveindicatedthattheratesofbothosteosisandboneabsorptioninMMarehigherthanthoseinhealthycontrols.Furthermore,therateofboneabsorptionisfrequentlyfasterthanthatofboneformationinMM;BonedestructioninMMresultsfromimbalancebetweenanabolismandcatabolisminbonetissueofthepatients.Bonemetabolisminvolvestwocomponentsinbonetissue:bon…     

Urinary type Ⅳ collagen: a specific indicator of incipient diabetic nephropathy

ＤｉａｂｅｔｉｃｎｅｐｈｒｏｐａｔｈｙｉｓｏｎｅｏｆｔｈｅｍａｊｏｒｃｏｍｐｌｉｃａｔｉｏｎｓｏｆｄｉａｂｅｔｅｓａｎｄｈａｓｂｅｃｏｍｅｔｈｅｍａｉｎｃａｕｓｅｏｆｅｎｄｓｔａｇｅｒｅｎａｌｄｉｓｅａｓｅｉｎｔｈｅＵＳＡ Ｍｏｇｅｎｓｏｎ1　ｒｅｐｏｒｔｅｄｔｈａｔ 80 %ｏｆｐａｔｉｅｎｔｓｗｉｔｈｉｎｓｕｌｉｎ ｄｅｐｅｎｄｅｎｔｄｉａｂｅｔｅｓｍｅｌｌｉｔｕｓａｎｄ 2 2 %ｏｆｐａｔｉｅｎｔｓｗｉｔｈｎｏｎ ｉｎｓｕｌｉｎ ｄｅｐｅｎｄｅｎｔｄｉａｂｅｔｅｓｍｅｌｌｉｔｕｓｐｌｕｓｍｉｃｒｏａｌｂ…     

Modulation of Matrix Metalloproteinase and TIMP-1 Expression by TGF-β1 in Cultured Human RPE Cells

Matrix metalloproteinases(MMPs)are a familyof zinc binding,calcium-dependent endopeptidases thatfunction by degrading extracellular matrix(ECM)components.The functional effects of these enzymesare in part controlled byinteractions withtissueinhibi-tors of metalloproteinases(TI MPs)acting as naturalMMPinhibitors.Aprecise balance between MMPandTI MPactivities may be i mportant for the integrity ofECMcomponents[1].It shows that the expression andactivity of MMPs could be regulated by va…     

TGF-beta1 Transgenic Mouse Model of Thoracic Irradiation: Modulation of MMP-2 and MMP-9 in the Lung Tissue

TGF-β1has been shown to play a key role inthe development and progression of radiation-in-duced lung injury and subsequent fibrosis[1].Re-modeling of the lung is a hall mark of radiation-in-ducedlunginjury andinvolves extensive alterationsof lung extracellular matrix(ECM).MMPs are afamily of matrix degrading proteinases with struc-tural si milarities,and their activity is specificallyinhibited by the tissueinhibitors of metalloprotein-ases(TI MPs).In the present study,we intend toinvestig…     

Effect of IFN-γ, IL-4 on proliferation and synthesis of hyaluronic acid and collagen in cultured human retroorbital fibroblasts in vitro

Objective To investigate the cellular immune mechanism of thyroid associated ophthalmopathy (TAO) and provide a basis for treating TAO with cytokine or anti-cytokine agents, we determined whether interferon (IFN)-γ and interleukin (IL)-4, representative cytokines of Th1 and Th2 cells, may have some effect on the development and progression of TAO.Method Retroorbital fibroblasts (RF) proliferation and the synthesis of hyaluronic acid (HA) and type Ⅳ collagen were measured with liquid scintillation and radioimmunoassay. Results IFN-γ stimulated RF proliferation and HA synthesis and had a significant inhibitory effect on type Ⅳ collagen synthesis. IL-4 stimulated proliferation and type Ⅳ collagen synthesis in RF and had inhibitory effect on HA synthesis. When IFN-γ (100U/ml) and IL-4 (1μg/L) were incubated together with RF, they antagonized their respective stimulatory or inhibitory effect on the proliferation and synthesis of HA and type Ⅳ collagen. Thyrotropin (TSH) stimulated RF proliferation and type Ⅳ collagen synthesis in a dose-dependent manner, while only at high dose (100U/L and 200U/L), stimulated RF to synthesize HA. Conclusions IFN-γ, a representative cytokine of Th1 cells, is responsible for the inflammatory process of TAO; whereas IL-4, a representative cytokine of Th2 cells, has some effect on the repair process. IL-4 could antagonize the inflammatory effect of IFN-γ on RF. TSH may have aggravating effect on the pathogenesis of TAO.     

Expressions of cyclin E, cyclin dependent kinase 2 and p57~(KIP2) in human gastric cancer

Ｔｈｅｍｏｒｂｉｄｉｔｙａｎｄｍｏｒｔａｌｉｔｙｏｆｇａｓｔｒｉｃｃａｎｃｅｒｈａｖｅｄｅｃｒｅａｓｅｄｍａｒｋｅｄｌｙｓｉｎｃｅｔｈｅ 1930’ｓ 1　Ａｌｔｈｏｕｇｈｔｈｉｓｄｅｃｒｅａｓｅｈａｓｏｃｃｕｒｒｅｄｗｏｒｌｄｗｉｄｅ ,ｔｈｅｍｏｒｂｉｄｉｔｙａｎｄｍｏｒｔａｌｉｔｙｏｆｇａｓｔｒｉｃｃａｎｃｅｒａｒｅｓｔｉｌｌｃｏｍｐａｒａｔｉｖｅｌｙｈｉｇｈｅｒｉｎＪａｐａｎ ,Ｃｈｉｎａ ,Ｃｈｉｌｅ ,ａｎｄＩｒｅｌａｎｄ Ｇａｓｔｒｉｃｃａｎｃｅｒｉｓｓｔｉｌｌｔｈｅｌｅａｄｉｎｇｃａｕｓｅｏｆｃ…     

Effects of Icariin on Expression of OPN mRNA and Type ⅠCollagen in Rat Osteoblasts in Vitro

Osteopontin(OPN)isagroupofactivepro teinswhichareproducedbybonetissue.OPNcanregulatethelocalfunctionandplayanimportantroleinconstructionandremodelingofbone.typeⅠcollagenisthemaincomponentinbonematrixwhichplaysroleinbonerestoration.Osteoporosisiscausedbyboneresorptionmorethanbonefor mationandosteoblastsarethefunctionalcellswhichareresponsibleforboneformation.Thisstudywasdesignedtoshowthemolecularmecha nismsofIcariinanditseffectonexpressionofOPNmRNAandtypeⅠcollageninratosteoblastsinvitroa…     

Inhibition of α_1(Ⅰ) collagen gene in vitro transcription by antisense oligodeoxynucleotides

Tab I collagen is an ~ component of etri~ Inatrices and edestS in a Vallety Of hssues and or~ such as the skin, ho, tendon etC[l'2]. It is oompe Of 2 al chains and I ac chain which interact witheach other to form a characteristic triple hells. The abnorInality Of ac 1 collagen is Often caused by mUtation or abnonhal ~ Of one Of its geneS, halting in cof itS Physiolopcal abationS[3-6].Antisense nucleic aCids are ethehve in ~the~ or UnoontIDlled gene ~on. aam stlatng OfhaCription blwha…     

Expression of hypoxia-inducible factor 1α in human normal, benign, and malignant prostate tissue

Objective To investigate hypoxia-inducible factor 1α (HIF-1α) protein expression in normal prostates (NP), benign prostatic glandular hyperplasia (BPH), and prostate adenocarcinoma (Pca).Methods HIF-1α protein expression was determined by immunohistochemistry in formalin-fixed and paraffin-embedded specimens obtained from 13 cases of NP, 28 cases of BPH, and 34 cases of Pca. In cases of Pca, the relationship between HIF-1α protein expression and certain clinicopathological factors, such as clinicopathologic stage and Gleason score, was evaluated. Results NP manifested no immunoreactivity, whereas Pca and BPH showed significantly increased HIF-1α protein expression. A significantly higher expression was observed in Pca specimens compared with BPH samples. In Pca, no significant relationship between HIF-1α protein expression and clinicopathological factors was found. Conclusion Our findings of increased HIF-1α protein expression in BPH and Pca specimens suggests the potential role of this protein in BPH and Pca.     

Effects of endothelin B receptor antagonists, BQ788 and ET-1_(11-21) fragment on the bronchoconstriction elicited by isocapnic hyperpnea in guinea pigs

Ｅｎｄｏｔｈｅｌｉｎ (ＥＴ)ｗａｓｏｒｉｇｉｎａｌｌｙｉｄｅｎｔｉｆｉｅｄｉｎ 1988ａｓａｖａｓｏｃｏｎｓｔｒｉｃｔｏｒｃｏｍｐｏｕｎｄｉｎｔｈｅｃｕｌｔｕｒｅｓｕｐｅｒｎａｔａｎｔｏｆｐｏｒｃｉｎｅａｏｒｔｉｃｅｎｄｏｔｈｅｌｉａｌｃｅｌｌｓ 1　ＥＴｓ (ＥＴ 1,ＥＴ 2ａｎｄＥＴ 3)ａｒｅ 2 1ａｍｉｎｏａｃｉｄｐｅｐｔｉｄｅｓ 2 　ＮｕｍｅｒｏｕｓｃｅｌｌｓｓｙｎｔｈｅｓｉｚｅａｎｄｒｅｌｅａｓｅＥＴｓ ,ｉｎｃｌｕｄｉｎｇｍａｉｎｌｙＥＴｃｅｌｌｓ ,ｂｕｔａｌｓｏｈｕｍａｎｉｓｏｌａｔｅｄｂｒｏｎｃ…     

Effect of angiotensin Ⅱ and angiotensin Ⅱ type 1 receptor antagonist on the proliferation,contraction and collagen synthesis in rat hepatic stellate cells

Background Angiotensin Ⅱ （Ang Ⅱ） is a very important vasoactive peptide that acts upon hepatic stellate cells （HSCs）, which are major effector cells in hepatic cirrhosis and portal hypertension. The present study was aimed to investigate the effects of Ang Ⅱ and angiotensin Ⅱ type 1 receptor antagonist （AT1RA） on the proliferation, contraction and collagen synthesis in HSCs.
Methods HSC-T6 rat hepatic stellate cell line was studied. The proliferation of the HSC cells was evaluated by MTT colorimetric assay while HSC DNA synthesis was measured by ^3H-thymidine incorporation. The effects of angiotensin Ⅱ and AT1RA on HSCs contraction were studied by analysis of the contraction of the collagen lattice. Cell culture media were analyzed by RT-PCR to detect secretion of collagen Ⅰ （Col Ⅰ）, collagen Ⅲ （Col Ⅲ） and transforming growth factor β1 （TGF-β1） by enzyme linked immunosorbent assay. HSC was harvested to measure collagen Ⅰ, collagen Ⅲ and tissue inhibitor of metalloproteinase-1 （TIMP-1） mRNA expression.
Results Ang Ⅱ （（1×10^-10-1×10^-4）mol/L）stimulated DNA synthesis and proliferation in HSCs compared with untreated control cells. AT1RA inhibited angiotensin Ⅱ induced proliferation of HSCs. A linear increase in the contractive area of collagen lattice correlated with the concentration of angiotensin Ⅱ （1×10^-9-1×10^-5 mol/L） and with time over 48 hours. AT1RA blocks angiotensin Ⅱ induced contraction of collagen lattice. Col Ⅰ, Col Ⅲ and TGF-β1 levels of the Ang Ⅱ group were higher than those of control group and this increase was downregulated by AT1RA. The mRNA expressions of Col Ⅰ, Col Ⅲ and TIMP-1 were higher in HSCs from the Ang Ⅱ group than the control group and downregulated by AT1RA.
Conclusions Angiotensin Ⅱ increased DNA synthesis and proliferation of HSCs in a dose-dependent manner, stimulated the contraction of HSCs dose- and time-dependently. Angiotensin also promoted excretion of Col I, Col Ⅲ and TGF-β1 lev     

Do methylenetetrahydrofolate dehydrogenase,cyclohydrolase, and formyltetrahydrofolate synthetase 1 polymorphisms modify changes in intelligence of school-age children in areas of endemic fluorosis?

Background: Excessive exposure to fluoride can reduce intelligence. Methylenetetrahydrofolate dehydrogenase, cyclohydrolase, and formyltetrahydrofolate synthetase 1 (MTHFD1) polymorphisms have important roles in neurodevelopment. However, the association ofMTHFD1 polymorphisms with children’s intelligence changes in endemic fluorosis areas has been rarely explored.Methods: A cross-sectional study was conducted in four randomly selected primary schools in Tongxu County, Henan Province, from April...     

Relationship between the burden of pneumocystis carinii, the inflammatory reaction and lung injury in pneumocystis carinii pneumonia

Objective To study the relationship between the burden of Pneumocystis carinii (P. carinii) and the inflammatory reaction and biochemical markers in bronchoalveolar lavage fluids (BALF)in a rat model of P. carinii pneumonia (PCP). Methods Clean grade 50 male Sprague-Dawley rats were immunosuppressed by a subcutaneous injection of 25mg cortisone acetate twice a week for 8-12 weeks; the PCP model was successfully induced in 14 rats. The inflammatory reaction and biochemical markers of the activity of lactate dehydrogenase (LDH), alkaline phosphatase (AL P) and type Ⅳ collagenase (matrix metalloproteinases, MMP-2, MMP-9) as well a s the values of total protein (TP) and albumin (ALB) in BALF between the mild burden group of P. carinii (involved alveoli <25% per 100 alveoli, G roup A) and the moderate to severe burden group (involved alveoli ≥25% per 100 alveoli, Group B) were measured. The other six clean grade SD rats served as no rmal control group (Group C).Results The total white cell count in BALF was higher in Group B ［(6.8±1.7)×10(6)/L ］ than in Group A ［(3.8±1.2)×10(6)/L］ (P<0.01); however, there were no differences in white cell differentiation. Assays of biochemical marke rs showed that ALB in BALF in Group B (0.893±0.469 g/L) was increased in com parison with Group A (0.262±0.169 g/L); it was only 0.026±0.021 g /L i n Group C. The contents of TP and activities of LDH were higher in Group B (TP 1.756±0.706 g/L, LDH 2580±550 U/L) than in Group A (TP 0.784±0.553 g/L, LDH 1410±620 U/L); the values of TP and LDH were 0.063±0.020 g/L an d 370±250 U/L respectively in Group C. The activity of Type Ⅳ collagenase, including MMP-2 and MMP-9, was higher in Group B than in Group A (P<0.0 1) (MMP-2: 1102±169 grey value vs 459±274 grey value; MMP-9: 1218±257 grey value vs 449±225 grey value). There was no activity of Type Ⅳ collagenase in BALF of Group C. No statistically significant difference was observed in ALP between the groups B and A. Conclusions These results indicate that there is a significant correlation between the burde n of P. carinii in lung tissues and the inflammatory reaction as well as bi ochemical markers of the resultant activity of lung injury.