基质金属蛋白酶-2、-9及其组织抑制因子（TIMPs）在动情周期大鼠子宫中的表达

基质金属蛋白酶（MMPs)家族的作用是降解所有细胞外基质,其活性受其特异性组织抑制因子（TIMPs)的抑制。细胞外基质成分的降解与重组在动物生殖生长过程中起重要作用,其变化可以通过MMPs和TIMPs两者表达水平的变化进行监测。大鼠虽然没有月经形成,但是在其子宫内膜也出现类似灵长类的生殖生物学变化。本文从MMPs和TIMPs两者的表达水平,对大鼠子宫内膜的这些变化进行了研究。于大鼠动情周期的不同时期,将算处死,取子宫制备酶粗提液和组织切片,采用酶谱法(zymography)和原位杂交方法研究动情周期大鼠子宫中MMP-2和-9的活性变化以反MMP-2、-9和TIMP-1、-2、-3mRNA的表达。并通过光密度扫描方法对酶谱结果进行半定量分析。所用杂交探针见Table 1．酶谱结果显示：在动情周期大鼠子宫中只检测到67kDa的MMP-2活性,而没有检测到MMP-9的活性(Fig.1)。MMP-2的活性在动情前期最高,动情期和动情后期次之,同情期最低(Flg．2)。原位杂交结果显示：MMP-2、-9、TIMP-1、-2、-3m RNA主要在子宫内膜基底部的基质细胞中表达。MMP-2和-9 mRNA在动情前期、动情期和动情后期子宫内膜基底部的基质细胞和动情期子宫环行肌层中表达均较强,在间情期表达较弱。MMP-9 mRNA在动情期腔上皮和腺上皮细胞中也有较弱的表达(Fig．3)。TIMP-1 mRNA在动情期和动情后期子宫内膜基底部的基质细胞中以及动情期腔上皮和腺上皮细胞中表选较强,在动情前期和间情期表达较弱(Fig．4)。TIMP-2 mRNA在动情期和间情期子宫内膜基底部的基质细胞中以度在动情期上皮细胞中表达较强,在动情前期和动情后期表逮较弱(Fig.4)。TINP-3 mRNA在动情期子宫内膜基底部的基质细胞中表达最强,在动情后期和间情期次之,动情前期表达最弱。TIMP-3 mRNA在动情期子宫环行肌层中也有较强的表达(Fig.5)。由此可见,MMP-2的活性和MMIP-2的基固表达基本一致,MMP-2和-9及其组织抑制因子TIMPs在时间和空间上的表达也基本一致。提示：MMP-2,-9及TIMP-1、-2、-3共同参与了动情周期大鼠子宫内膜的周期性变化。     

RT—PCR测定大鼠妊娠早期子宫孕激素受体基因的表达

孕激素在妊娠的建立和维持过程中起着非常重要的作用,但目前为止未见有关大鼠子宫 激素受体（ＰＲ）基因在该过程中表达情况的系统报道。本和反转偶联聚合酶链式反应（ＲＴ－ＰＣＲ）方法测定了大鼠动情周期和妊娠早期子宫孕激素受体基因的转录,结果表明：１．动情周期中,子吕ＰＲｍＲＮＡ水平在动情期最高,在动情后期最低,动情期水平约为动情后期的２倍。２．妊娠开始后,子宫ＰＲｍＲＮＡ水平迅速上地ｄ３－ｄ４（着床前）达     

大鼠肝生长发育过程中ACP、AKP、HSC70/HSP68和PCNA的变化(英文)

磷酸酶（ＡＣＰ、ＡＫＰ）在生物的机能分化中起重要作用,热休克蛋白（ＨＳＰｓ）是近几年发现的一类在胚胎发育、细胞生存中起重要作用的分子,无论是胚胎发育还是细胞结构和功能构建都和细胞增殖密切相关,增殖细胞核抗原（ＰＣＮＡ）是检测细胞增殖的良好指标。 本实验用组织化学、免疫组织化学、Ｗｅｓｔｅｒｎ印迹、酶的原位复性电泳、体视学分析等方法定性和定量分析了酸性磷酸酶（ＡＣＰ）（Ｆｉｇ．１＆２）、碱性磷酸酶（ＡＫＰ）（Ｆｉｇ．４＆５）、构成性热休克蛋白 ７０／诱导性热休克蛋白 ６８（ＨＳＣ７０／ＨＳＰ６８）（Ｆｉｇ．６）和ＰＣＮＡ（Ｆｉｇ．７＆８, Ｔａｂｌｅ１）在大鼠肝生长发育（从１４天胚胎到成体）过程中的动态变化。结果表明：（１）在大鼠肝生长发育过程中,ＡＣＰ有两个活性高峰期,其时段处于大鼠吃奶和吃饲料起始期（Ｆｉｇ．１＆２）;（２）在ＡＣＰ的第一个活性高峰期时,ＡＫＰ活性降低;而在ＡＣＰ的第二个活性高峰期时,正值ＡＫＰ的活性高峰期（Ｆｉｇ．３）;（３）ＡＣＰ活性高峰期也是ＰＣＮＡ含量高峰期;（４）ＨＳＣ７０／ＨＳＰ６８在刚断奶的幼鼠肝和成体肝中表达量较多,其他时段表达极少。根据上述结果推测：ＡＣＰ和ＰＣＮＡ通过调节细     

大鼠动情周期及妊娠早期卵巢中明胶酶A活性变化

用酶谱法测定了大鼠动情周期以及正常妊娠早期和假孕早期不同时间卵巢中明胶酶Ａ活性的变化,并观察了甾体激素对明胶酶Ａ活性变化的影响,结果表明：在不同的周期及妊娠期卵巢中均存在６７ｋＤ为主的明胶酶Ａ,但未发现有明胶酶Ｂ存在。明胶酶Ａ活性变化如下：１）在大鼠的动情前期明胶酶Ａ的活性最高,间情期最低;２）在妊娠早期（１－７天）的卵巢中,明胶酶Ａ的活性在妊娠第４天达到最高,第１－３天及第５、６天其活性也较高,     

HSP_(70)基因表达对高粱育性的影响(英文)

高粱细胞质雄性不育系３１９７Ａ（３Ａ）在常温条件下是不育的（Ｆｉｇｓ．１１＆２）,经热激（４５℃）诱导不同程度地恢复了育性（Ｆｉｇｓ．１３＆４）,为研究其不育机理提供了线索。热激２ｈ后,３Ａ中即可产生一类线粒体热激蛋白（ＨＳＰｓ）。其中,分子量为７０ｋＤ的ＨＳＰ７０含量最高,也最为稳定。不过,３Ａ中ＨＳＰｓ的稳定性弱于保持系３１９７Ｂ（３Ｂ）（Ｆｉｇ．２,Ｐａｎｅｌｓ１～４）。放线菌素Ｄ抑制ＨＳＰｓ的合成,而氯霉素无此作用（Ｆｉｇ．２,Ｐａｎｅｌｓ５＆６）,表明：ＨＳＰｓ是由核基因编码、在细胞质中合成、再跨膜转运到线粒体中的。３Ａ幼穗经热激后,线粒体的总蛋白量猛增了２．７倍（Ｆｉｇ．３）,达到３Ｂ的水平,育性亦变为可育的。Ｆｉｇ．４表明：ＨＳＰ７０反义链ｃＤＮＡ（Ｒ１）能进入到３Ｂ花药细胞中,并与靶ＲＮＡ（ＨＳＣ７０ｍＲＮＡ）结合,而对照、正义链ｃＤＮＡ（Ｄ）链无此反应。由此、再增加一个通用保守序列的反义链ｃＤＮＡ（Ｒ２）、共两个探针（Ｒ１、Ｒ２）,可以检测到：３Ａ在常温下没有能力合成ＨＳＣ７０ｍＲＮＡ（Ｆｉｇ．５）,而在热激条件下,转变为有能力（Ｆｉｇ．６）。启示：３Ａ在热激条件下由不育转变为可育     

胶原酶-3活性在大鼠动情周期及胚泡着床中的变化(英文)

大鼠动情周期以及胚胎着床过程中,子宫内膜会发生结缔组织的降解与重构。胶原酶3（MMP－13）是降解纤维类胶原的主要蛋白水解酶类之一。其活性在这些过程中的变化值得研究。采用液体闪烁计数测定~3H标记胶原的方法,对大鼠动情周期及早期妊娠子宫中胶原酶-3（MMP－13）的活性进行了测定。结果表明：在动情周期中;激活型MMP－13在间情期最低,酶原型及激活型的MMP－13在动前期达高峰,动情后期酶原型和激活型MMP也明显高于间情期（P＜0.05）（Fig．1）。妊娠第1、2天酶原型的MMP-13的活性显著高于第3～7天,第3、4天酶原型和激活型MMP-13的活性均低于妊娠第1、2天（P＜0.05）;而第5天酶原型MMP-13的活性却显著高于第4、6两天（P＜0．05）;激活型MMP－13的活性也高于第4天（P＜0．05）（Fig．2）。着床部位酶原型MMP－13的活性明显高于非着床部位（P＜0．05）,而激活型MMP－13的活性则无明显差异（P＞0．05）（Fig．3）。大鼠假孕早期子宫中MMP－13的活性变化与正常早期妊娠相似,但其活性却明显低于正常早期妊娠（Fig．4）。结果提示：大鼠子宫中MMP-13参与大鼠动情周期及早期妊娠过程,尤其是在胚胎着床过程中可能起着重要作用。     

血管紧张素Ⅱ对大鼠心肌肌浆网Ca~(2+),Mg~(2+)-ATPase基因转录调节的影响

观察血管紧张素Ⅱ（ＡｎｇⅡ）对心肌肌浆网Ｃａ２＋,Ｍｇ２＋－ＡＴＰａｓｅ基因（ＳＥＲＣＡ２ａ）转录调节的影响,评价ＤＭＰ８１１对此效应的干预作用．６周龄雄性ＳＤ大鼠随机分为３组,每组６只．组１：生理盐水输注;组２：ＡｎｇⅡ输注＋ＤＭＰ８１１管饲（３ｍｇ·ｄ－１·ｋｇ－１）;组３：ＡｎｇⅡ输注（２００ｎｇ·ｍｉｎ－１·ｋｇ－１．１周后称其体重,取心脏并称重,提取心脏总ＲＮＡ后采用Ｎｏｒｔｈｅｒｎｂｌｏｔ的方法检测ＳＥＲ－ＣＡ２ａ的转录水平,采用ＲＴ－ＰＣＲ检测ＡｎｇⅡ１型受体（ＡＴ１）ｍＲＮＡ水平．实验后,组３心重（ＣＷ）、心重／体重（Ｃ／Ｂ）、ＡＴ１受体转录水平均高于组１（分别增加４．７±０．４％,４．９±０．９％和２４．７±３．５％;Ｐ＜０．０１）,而ＳＥＲＣＡ２ａ基因转录水平显著低于组１（降低２０．１±３．０％,Ｐ＜０．０１）,并且ＳＥＲＣＡ２ａｍＲＮＡ水平与ＡＴ１受体ｍＲＮＡ水平呈负相关（ｒ＝－０．７４,Ｐ＜０．０１）．ＡｎｇⅡ导致的上述改变能被ＤＭＰ８１１完全阻断．ＡｎｇⅡ通过其Ⅰ型受体的介导,诱导了ＳＥＲＣＡ２ａ的转录下调     

动情周期中大鼠输卵管上皮凝集素受体的研究

大鼠动情周期包括动情前期（ＰＥ）、动情期（Ｅ）、动脉后期（ＭＥ）和动情间期（ＤＥ）。采用生物素标记的５种凝集素（ＣｏｎＡ、ＰＮＡ、ＲＣＡ、ＵＥＡ－Ｉ以及ＷＧＡ）对大鼠动情周期中输卵管上皮细胞的凝集素受体进行了研究,发现在大鼠动情周期中输卵管粘膜上皮细胞凝集素受体均有不同程度的变化：其中,ＣｏｎＡ的阳性反应以ＰＥ组最强,ＤＥ组最弱（Ｐ＜０．０１）;ＰＮＡ的阳性反应以Ｅ组最强,ＤＥ组为阴性;ＲＣＡ的阳性反应强度以ＰＥ和Ｅ组最强,ＤＥ组最弱（Ｐ＜０．０１）;ＵＥＡ－Ⅰ的阳性反应颗粒可见于动情周期各期,但以ＰＥ组为强（Ｐ＜０．０１）,其它各期间的反应强度差异无显著性（Ｐ＞０．０５）;ＷＧＡ的阳性反应以ＤＥ组最强,与其它各组比较,差异有高度显著性（Ｐ＜０．０１）,其它各组之间阳性反应强度差异无显著性（Ｐ＞０．０５）。说明输卵管上皮细胞的糖组分在动情周期中发生了某些变化。推测这些变化有利于输卵管功能活动的进行     

大鼠动脉内膜损伤后血管中的骨桥蛋白和基质Gla蛋白mRNA的表达变化

本实验采用球囊剥脱大鼠主动脉内皮造成血管内膜损伤的芭Ｎｏｒｔｈｅｒｎ印迹分析,逆转录聚合酶链式反应（ＲＴ－ＰＣＲ）等方法,研究大鼠主动脉内损伤后血管中的骨桥蛋白（ｏｓｔｅｏｐｏｎｔｉｎ,ＯＰＮ）和基质Ｇｌａ蛋白（ｍａｔｒｉｘ Ｇｌａ ｐｒｏｔｅｉｎ,ＭＧＰ）ｍＲＮＡ水平的动态变化。与无内皮损伤血管比较,损伤后的血管中ＯＰＮ和ＭＧＰ的ｍＲＮＡ水平明显升高,损伤后１,７,１４ｄ,两者的ｍＲＮＡ水平逐渐     

人主动脉硫酸乙酰肝素蛋白聚糖对培养的人血管壁细胞生长的作用

通过培养的人主动脉平滑肌细胞（ｈＡＳＭＣ）及脐静脉内皮细胞（ｈＵＶＥＣ）,应用３Ｈ－ＴｄＲ参入、Ｎｏｒｔｈｅｒｎｂｌｏｔ分析、逆转录多聚酶链反应（ＲＴ－ＰＣＲ）、放射免疫分析（ＲＩＡ）、和紫外比色法等技术观察了人主动脉中硫酸乙酰肝素蛋白聚糖（ＨＳＰＧ）对ｈＡＳＭＣ和ｈＵＶＥＣＤＮＡ合成的作用及对血小板源生长因子（ＰＤＧＦ）、ＰＤＧＦ受体、转化生长因子β（ＴＧＦ－β）、内皮素－１（ＥＴ－１）或碱性成纤维细胞生长因子（ｂＦＧＦ）基因表达和肾素－血管紧张系统（ＲＡＳ）的影响,结果显示,ＨＳＰＧ明显抑制培养的ｈＡＳＭＣ基础的ＤＮＡ合成（ｃｐｍ值为：１０３８５±３２６３ｖｓ,２５５４１±６４２１,Ｐ＜０．０１）及外源性ＰＤＧＦ诱导的ＤＮＡ合成（ｃｐｍ值为：９８７８±１９４７ｖｓ．１３４８１±４４ｌ０,Ｐ＜０．０５）;抑制ＰＤＧＦＡ链、ＴＧＦ－Ｂｐ和ＥＴ－１ｍＲＮＡ表达,提高ＰＤＧＦａ和β受体ｍＲＮＡ的表达;显著降低ｈＡＳＭＣ培养液中血管紧张素Ⅱ（ＡｎｇⅡ）的浓度和血管紧张素转换酶（ＡＣＥ）的活性,推测ＨＳＰＧ抑制ＰＤＧＦＡ链、ＴＧＦ－β及ＥＴ－１ｍＲＮＡ表达,降低ＡＣＥ活性及ＡｎｇⅡ浓度是其抑制ｈＡＳＭＣ增殖的重要机     

Expression of Smad2 and Smad4, transforming growth factor-beta signal transducers in rat endometrium during the estrous cycle, pre-, and peri-implantation

SMADs are intracellular signaling molecules that transmit signals elicited by members of transforming growth factor-β (TGF-β) superfamily. To decipher the mechanism of TGF-β signaling during the estrous cycle and implantation, we performed in situ hybridization to investigate the expression patterns of mRNAs for Smad2 and Smad4 in rat endometrium during the estrous cycle and on Days 0.5, 1.5, 2.5, 3.5, 4.5, 5.5, and 6.5 of pregnancy. Intense epithelial expression of Smad2 mRNA at diestrus and proestrus was reduced at estrus and metaestrus, while Smad4 maintained its constitutive expression during the estrous cycle. During pre-implantation, both Smads were accumulated in the luminal epithelium and the glandular epithelium. Contrary to the dramatic Smad4 expression, Smad2 was highly down-regulated on Day 2.5 and was increased on Day 3.5. During peri-implantation, both Smads were expressed in the luminal epithelium, subepithelial stroma, and the primary decidual zone. Smad4 was down-modulated on Day 5.5. These results suggest that (a) both Smads are involved in the tissue remodeling of cycling and pregnant rat uteri; (b) TGF-β signaling functions mainly in the epithelium during pre-implantation and Smad2 is involved in the endometrial switch from the neutral phase to the receptive phase; (c) TGF-β signaling is down-regulated at the time when trophoblast invasion begins and both Smads are involved in the formation of the primary decidual zone.     

Cyclic changes in the uterine phosphatases of Suncus murinus sindensis Anderson, the Indian common house shrew.

Cyclic changes in the phosphatases were studied histochemically in the uterine complex of the female Suncus. Alkaline phosphatase activity showed constant and predictable changes in the various phases of the cycle with the maximum activity during metaestrus. Acid phosphatase and ATPase activities also showed constant changes with moderate activity during diestrus and proestrus but with maximal activities during estrus and metaestrus. No proper localization of the enzyme is discernible in the case of G-1-Pase and G-6-Pase.     

Expression of matrix metalloproteinase -2, -9 and tissue inhibitors of metalloproteinase -1, -2, -3 mRNAs in rat uterus during early pregnancy

Zymography and in situ hybridizition were used to investigate matrix metalloproteinase-2, -9 (MMP-2, -9) activities, and expression of mRNAs for MMP-2, -9 and tissue inhibitors of matrix metalloproteinases (TIMP-1, -2, -3) in the rat uterus during early pregnancy (day 1-7). The zymography results showed two forms of MMP-2 (64 and 67 kDa) in the rat uteri during early pregnancy. The 64-kDa MMP-2 activity was the highest on day 2 (P < 0.01) and higher on day 5 and 6 (P < 0.05). The 67-kDa MMP-2 activity reached the highest on day 5 and 6 (P < 0.01). The 64-kDa MMP-2 activity at the implantation sites was higher than those at interimplantation sites (P < 0.05). Furthermore, the 67 kDa MMP-2 can be converted to 64 kDa forms by incubation with p-aminophenylmercuric acetate (APMA) and trypsin in vitro. The 92-kDa MMP-9 activity was only detected on day 5 and 6 of pregnancy (P < 0.01). In situ hybridization showed that on day 1-4 of pregnancy, both MMP-2 and TIMP-2 mRNAs were evidently localized in the basal stromal cells. On day 5, MMP-2 mRNA signals were decreased in the basal stromal cells and mRNA for TIMP-2 was expressed in the epithelial cells and subepithelial stromal cells. The mRNAs for MMP-9, TIMP-1, and -3 were mainly expressed in epithelial cells on day 1-5. At the implantation site on day 6, the mRNAs for MMP-2, -9, TIMP-1, -2, and -3 were highly expressed in the primary decidual zone surrounding the implanting embryo, and in the whole decidualized stromal cells (the primary and secondary decidual zones) at the implantation site on day 7. The intensities of mRNAs for the TIMPs in decidualized stromal cells at the implantation site on day 6 and 7 were stronger than those for the MMPs. The weak mRNAs for MMP-2, -9, TIMP-1, and -3 but not TIMP-2 were also observed in the ectoplacental cone/trophoblastic cells of the implanting embryos. However, at the interimplantation sites on day 6 and 7, MMP-2, -9, TIMP-1, -2, and -3 mRNAs were weakly expressed in the epithelial cells, subepithelial stromal cells, and myometrium. The results suggested that the implanting rat embryo strongly induced MMP-2 and -9 proteins and gene expression for decidulization and embryo invasion, which were strictly controlled and balanced by the simultaneous expression of TIMP-1, -2 and -3.     

Temporal and spatial expression of MMP-2,-9,-14 and their inhibitors TIMP-1,-2,-3 in the corpus luteum of the cycling rhesus monkey

A CL develops by extensive cellular reorganization and neovascularization of the remnants of the evacu-ated follicle following ovulation. In both rodent and primate, the development of CL is a rapid process with very high cellular turnover[1,2]. A CL is u…     

MMP-2、MMP-7、MMP-9、TIMP-1及TIMP-2在乳腺癌组织中的表达及意义

目的:探讨基质金属蛋白酶及其抑制剂在乳腺癌组织中的表达及其与肿瘤浸润转移的关系,为乳腺癌的临床治疗及预后预测提供基础。方法:选择我院2012年5月至2014年5月收治的乳腺癌患者80例,对所选病例的乳腺癌组织、癌旁组织及正常乳腺组织样本进行检测。观察并比较不同乳腺组织中MMP-2,MMP-7、MMP-9、TIMP-1及TIMP-2 m RNA的表达水平。结果:与正常乳腺组织相比较,乳腺癌组织和癌旁组织中MMP-2、MMP-7、MMP-9,TIMP-1及TIMP-2 m RNA的表达显著增加,差异具有统计学意义(P0.05)。乳腺癌组织中MMP-2、MMP-7、MMP-9、TIMP-1及TIMP-2 m RNA的表达显著高于癌旁组织和正常组织,差异具有统计学意义(P0.05)。随着肿瘤范围扩大,MMP-2、MMP-7和MMP-9 m RNA的表达水平显著增加(P0.05),而TIMP-1和TIMP-2 m RNA表达无显著变化(P0.05)。随着淋巴结转移进展,MMP-2、MMP-7和MMP-9 m RNA的表达显著增加(P0.05),而TIMP-1和TIMP-2 m RNA无显著变化(P0.05)。结论:MMP-2、MMP-7、MMP-9、TIMP-1和TIMP-2的m RNA在乳腺癌组织中呈高表达,这可能与乳腺癌的发生和发展有关,而MMP-2、MMP-7和MMP-9可能有助于预测乳腺癌的侵袭行为。     

Temporal and spatial expression of MMP-2,-9,-14 and their inhibitors TIMP-1,-2,-3 in the corpus luteum of the cycling rhesus monkey

The corpus luteum (CL) is a transient endocrine organ that secretes progesterone to support early pregnancy. If implantation is unsuccessful, luteolysis is initiated. Extensive tissue remodeling occurs during CL formation and luteolysis. In this study, we have studied the possible involvement of MMP-2,-9,-14, and their inhibitors, TIMP-1,-2,-3 in the CL of cycling rhesus monkey at various stages by in situ hybridization, immunohistochemistry and microscopic assessment. The results showed that the MMP-2 mRNA and protein were mainly expressed in the endothelial cells at the early and middle stages of the CL development, while their expressions were observed in the luteal cells at the late stage during luteal regression. MMP-9 protein was detected in the CL at the early and middle stages, and obviously increased at the late stage. The expressions of MMP-14 and TIMP-1 mRNA were high at the early and late stages, and low at the middle stage. TIMP-2 mRNA was high throughout all the stages, the highest level could be observed at the late stage. The TIMP-3 production was detected throughout all the stages, but obviously declined during CL regression. MMP-9,-14 and TIMP-1,-2,-3 were mainly localized in the cytoplasm of the steroidogenic cells. The results suggest that the MMP/TIMP system is involved in regulation of CL development in the primate, and the coordinated expression of MMP-2,-14 and TIMP-1,-3 may have a potential role in the CL formation and the functional maintaining, while the interaction of MMP-2,-9,-14 and TIMP-1,-2,-3 might also play a role in CL regression at the late stage of CL development in the primate.     

金属蛋白酶-2(MMP-2)和金属蛋白酶抑制因子(TIMP-1,-3)mRNA在小鼠胎盘中的表达

本实验利用原位杂交对小鼠妊娠不同时期胎盘中MMP－2,TIMP－2,－3mRNA的表达进行了研究。结果表明;MMP－2主要在具有很强的侵润能力的海绵滋养层细胞中表达,到妊娠13．5天时,MMP－2的表达明显降低,说明此时的滋养层细胞基本上失去侵润能力。TMIP－1和TMIP－3在滋养层细胞和蜕膜细胞中都有表达,这两种抑制因子的协同表达,一方面能够调控滋养层细胞侵入子宫内膜的深度,另一方面,滋养层细胞自身既表达MMP－2又表达TIMPs,可能对其自身有保护作用,使得MMP的水解功能局限于子宫蜕膜的特定区域。在妊娠10．5天,滋养层巨细胞同时表达TIMP－1,－3mRNA,这可能与其功能的转换是一致的;因为此时小鼠滋养层巨细胞体积最大,且不再增殖,同时其功能屯从侵入型向内分泌型转换。所以,MMPs和TIMPs在小鼠滋养层细胞和子宫蜕膜中的协同表达表明其在着床过程中可能发挥重要作用。     

Cell and agonist-specific regulation of genes for matrix metalloproteinases and their tissue inhibitors by primary glial cells

An imbalance in the matrix metalloproteinase (MMP) : tissue inhibitor of MMP (TIMP) ratio may be associated with tissue injury. Here, we studied the regulation of TIMP and MMP gene expression in primary glial cultures to ascertain the factors involved in the regulation of these genes in conditions of inflammatory neuropathology. Astrocytes were found to basally express TIMP-1 and TIMP-3 mRNA while microglia expressed only TIMP-2 mRNA. TIMP-4 mRNA was not detectable in either cell type. Treatment with interferon-alpha (IFN-alpha), IFN-gamma, interleukin-3 (IL-3), IL-6 or tumor necrosis factor-alpha (TNF-alpha) did not alter expression of the TIMP genes. However, in astrocytes, but not in microglia, serum, IL-1beta or lipopolysaccharide (LPS) evoked a dose- and time-dependent increase in TIMP-1 mRNA and a coincident down-regulation of the TIMP-3 gene. Astrocytes were found to express mRNA constitutively for MMPs -3, -11 and -14. In contrast, microglia expressed only MMP-12 mRNA under basal conditions. IL-1beta enhanced MMP-3 mRNA levels while LPS increased the MMP-3, -9, -12, -13 and -14 mRNAs. Our findings reveal that regulatory control of TIMP and MMP gene expression by glial cells is agonist- and cell-type specific, and suggest that innate immune signals govern the temporal and spatial expression patterns of TIMP and MMP genes in neuroinflammatory conditions of the CNS.