Zymography and in situ hybridization were used to investigate matrixmetalloproteinase -2, -9 (MMP -2, MMP-9) activities and expressions of MMP -2, -9 and TIMP1, -2, -3 (tissue inhibitors of matrix metallo-proteinases)...Zymography and in situ hybridization were used to investigate matrixmetalloproteinase -2, -9 (MMP -2, MMP-9) activities and expressions of MMP -2, -9 and TIMP1, -2, -3 (tissue inhibitors of matrix metallo-proteinases) mRNA in the rat uterus during estrouscycle. The relative activity was semiquanted by using densitometric analysis. The MMP-2(67 kDa) activity in every stage during estrpus cycle was detected by zymography. MMP-2activity was highest at proestrus; higher at estrus and metaestrus; lowest at diestrus. Throughin situ hybridization, MMP -2, -9, TIMP -1~ -3 mRNA mainly in hasal stroma cells of uterineendometrium were detected. The positive signals of MMP -2 and -9 mRNAs in hasal stromacells were shown stronger at proestrus, estrus and metaestrus while they showed the weakest atdiestrus. The expression of MMP -2 mRNA coincided with MMP -2 activity change. MMP-2and -9 mRNAs were also highly expressed in uterine circular muscle at estrus. Weak signals ofMMP -9 mRNA were detected in uterine luminal and glandular epithelial cells at estrus.TIMP -1 mRNA in hasal stroma cells was shown as the strongest expression at estrus andmetaestrus; stronger at proestrus and the weakest at diestrus. TIMP-2 mRNA in basal stromacells was stronger at estrus and diestrus; weaker at proestrus and metaestrus. TIMP -1 and -2mRNAs were also highly expressed in uterine luminal and glandular epithelial cells at estrus.TIMP -3 mRNA in hasal stroma cells revealed the strongest expression at estrus; stronger atdiestrus and metaestrus and showed the weakest at proestrus. The mRNA was also highlyexpressed in uterine circular muscle at estrus. In short, our present results provide evidencethat MMP -2, -9 and TIMP -1~ -3 were involved in rat uterine endometrium reconstructionduring estrous cycle.展开更多
AIM:To evaluate the protective role of AE-941,a matrix metalloproteinase(MMP) inhibitor,on ulcerative colitis(UC) in rats.METHODS:Sprague Dawley(SD) rats were randomly divided into three groups:a control group,an AE-9...AIM:To evaluate the protective role of AE-941,a matrix metalloproteinase(MMP) inhibitor,on ulcerative colitis(UC) in rats.METHODS:Sprague Dawley(SD) rats were randomly divided into three groups:a control group,an AE-941 treatment group,and an UC model group.Rats were sacrificed on days 7,21,or 56 following administration of treatment by enema and the disease activity index(DAI),colonic mucosa damage index(CMDI) and colonic expression of MMP-2 and MMP-9 were assessed.RESULTS:DAI and CDMI scores in the UC model group increased significantly compared to the control group at all timepoints(P < 0.001),and also increased significantly at the 21-and 56-d timepoints compared to the AE-941-treated group(DAI:21-and 56-d = 2.09 ± 0.25,1.52 ± 0.30 vs 1.55 ± 0.28,0.59 ± 0.19,respectively,P = 0.040 and 0.007,CMDI:21-and 56-d = 3.03 ± 0.42,1.60 ± 0.35 vs 2.08 ± 0.46,0.86 ± 0.37,respectively,P = 0.040 and 0.005).Furthermore,the colonic expression of MMP-2 and MMP-9 in the UC model group increased significantly compared to the control group(P < 0.001),and also increased compared to the AE-941-treated group on the 21-and 56-d timepoints(MMP-2:21-and 56-d = 0.6048 ± 0.0522,0.4163 ± 0.0330vs 0.3983 ± 0.0218,0.1093 ± 0.0072,respectively,P = 0.010;MMP-9:21-and 56-d = 0.6873 ± 0.0472,0.4328 ± 0.0257vs 0.5179 ± 0.0305,0.2673 ± 0.0210,respectively,P = 0.010 and 0.040).CONCLUSION:Expression of MMP-2 and MMP-9 increased significantly in rats with UC.AE-941 can reduce colonic mucosal damage by downregulating the expression of MMP-2 and MMP-9.展开更多
Despite the advent of improved surgical techniques and the development of cytotoxic chemotherapeutic agents useful for the treatment of colorectal cancer,the primary clinical challenge remains that of preventing and c...Despite the advent of improved surgical techniques and the development of cytotoxic chemotherapeutic agents useful for the treatment of colorectal cancer,the primary clinical challenge remains that of preventing and combating metastatic spread.Surgical resection is the best treatment for colorectal metastases isolated to the liver.However,in rodent models,the hepatic ischemia-reperfusion(I/R) applied during the surgery accelerates the outgrowth of implanted tumors.Among the adverse effects of I/R on cellular function,several studies have demonstrated an over expression of the matrix metalloproteinase-9(MMP-9) in the ischemic liver.Since several studies showed high local levels of expression and activity of this proteolytic enzyme in the primary colorectal adenocarcinoma,the role of MMP-9 might be considered as a potential common mediator,favoring both growth of local tumor and the dissemination of colorectal carcinoma metastases.展开更多
Effects of genistein on invasion and matrix metalloproteinase activities were investigated in HT1080 human sarcoma cells.Invasion of HT1080 cells through reconstituted basement membrane was inh...Effects of genistein on invasion and matrix metalloproteinase activities were investigated in HT1080 human sarcoma cells.Invasion of HT1080 cells through reconstituted basement membrane was inhibited when the cells were treated with 100 μ mol/L and 200 μ mol/L genistein.At the same concentrations,genistein not only suppressed latent forms of matrix metalloprotinese 2 and 9(MMP 2 and MMP 9) to convert into active forms,but also increase dramatically the tissue inhibitor of metalloproteinase(TIMP 1) mRNA contents and reverse the imbalance of MMPs and TIMPs.However,expressions of MMP 2 and MMP 9 were not significantly affected.Suppression of MMP activation and increase of TIMP 1 expression will decrease matrix degradation by MMPs,and consequently inhibit invasions of the cells.These results emphasized the existence of the imbalance between MMPs and TIMPs in tumor invasion and metastasis formation.The value of genistein as a drug for antiinvasion and anti metastasis chemotherapy was suggested.展开更多
文摘Zymography and in situ hybridization were used to investigate matrixmetalloproteinase -2, -9 (MMP -2, MMP-9) activities and expressions of MMP -2, -9 and TIMP1, -2, -3 (tissue inhibitors of matrix metallo-proteinases) mRNA in the rat uterus during estrouscycle. The relative activity was semiquanted by using densitometric analysis. The MMP-2(67 kDa) activity in every stage during estrpus cycle was detected by zymography. MMP-2activity was highest at proestrus; higher at estrus and metaestrus; lowest at diestrus. Throughin situ hybridization, MMP -2, -9, TIMP -1~ -3 mRNA mainly in hasal stroma cells of uterineendometrium were detected. The positive signals of MMP -2 and -9 mRNAs in hasal stromacells were shown stronger at proestrus, estrus and metaestrus while they showed the weakest atdiestrus. The expression of MMP -2 mRNA coincided with MMP -2 activity change. MMP-2and -9 mRNAs were also highly expressed in uterine circular muscle at estrus. Weak signals ofMMP -9 mRNA were detected in uterine luminal and glandular epithelial cells at estrus.TIMP -1 mRNA in hasal stroma cells was shown as the strongest expression at estrus andmetaestrus; stronger at proestrus and the weakest at diestrus. TIMP-2 mRNA in basal stromacells was stronger at estrus and diestrus; weaker at proestrus and metaestrus. TIMP -1 and -2mRNAs were also highly expressed in uterine luminal and glandular epithelial cells at estrus.TIMP -3 mRNA in hasal stroma cells revealed the strongest expression at estrus; stronger atdiestrus and metaestrus and showed the weakest at proestrus. The mRNA was also highlyexpressed in uterine circular muscle at estrus. In short, our present results provide evidencethat MMP -2, -9 and TIMP -1~ -3 were involved in rat uterine endometrium reconstructionduring estrous cycle.
基金Supported by Grants from Fund of the Education Department, Liaoning Province
文摘AIM:To evaluate the protective role of AE-941,a matrix metalloproteinase(MMP) inhibitor,on ulcerative colitis(UC) in rats.METHODS:Sprague Dawley(SD) rats were randomly divided into three groups:a control group,an AE-941 treatment group,and an UC model group.Rats were sacrificed on days 7,21,or 56 following administration of treatment by enema and the disease activity index(DAI),colonic mucosa damage index(CMDI) and colonic expression of MMP-2 and MMP-9 were assessed.RESULTS:DAI and CDMI scores in the UC model group increased significantly compared to the control group at all timepoints(P < 0.001),and also increased significantly at the 21-and 56-d timepoints compared to the AE-941-treated group(DAI:21-and 56-d = 2.09 ± 0.25,1.52 ± 0.30 vs 1.55 ± 0.28,0.59 ± 0.19,respectively,P = 0.040 and 0.007,CMDI:21-and 56-d = 3.03 ± 0.42,1.60 ± 0.35 vs 2.08 ± 0.46,0.86 ± 0.37,respectively,P = 0.040 and 0.005).Furthermore,the colonic expression of MMP-2 and MMP-9 in the UC model group increased significantly compared to the control group(P < 0.001),and also increased compared to the AE-941-treated group on the 21-and 56-d timepoints(MMP-2:21-and 56-d = 0.6048 ± 0.0522,0.4163 ± 0.0330vs 0.3983 ± 0.0218,0.1093 ± 0.0072,respectively,P = 0.010;MMP-9:21-and 56-d = 0.6873 ± 0.0472,0.4328 ± 0.0257vs 0.5179 ± 0.0305,0.2673 ± 0.0210,respectively,P = 0.010 and 0.040).CONCLUSION:Expression of MMP-2 and MMP-9 increased significantly in rats with UC.AE-941 can reduce colonic mucosal damage by downregulating the expression of MMP-2 and MMP-9.
基金Supported by The Swiss National Science Foundation,No. 32003B-134963/1,to Montecucco FEU FP7 Athero-Remo,No. 201668Swiss National Science Foundation,No. 310030B-133127,to Mach F
文摘Despite the advent of improved surgical techniques and the development of cytotoxic chemotherapeutic agents useful for the treatment of colorectal cancer,the primary clinical challenge remains that of preventing and combating metastatic spread.Surgical resection is the best treatment for colorectal metastases isolated to the liver.However,in rodent models,the hepatic ischemia-reperfusion(I/R) applied during the surgery accelerates the outgrowth of implanted tumors.Among the adverse effects of I/R on cellular function,several studies have demonstrated an over expression of the matrix metalloproteinase-9(MMP-9) in the ischemic liver.Since several studies showed high local levels of expression and activity of this proteolytic enzyme in the primary colorectal adenocarcinoma,the role of MMP-9 might be considered as a potential common mediator,favoring both growth of local tumor and the dissemination of colorectal carcinoma metastases.
文摘Effects of genistein on invasion and matrix metalloproteinase activities were investigated in HT1080 human sarcoma cells.Invasion of HT1080 cells through reconstituted basement membrane was inhibited when the cells were treated with 100 μ mol/L and 200 μ mol/L genistein.At the same concentrations,genistein not only suppressed latent forms of matrix metalloprotinese 2 and 9(MMP 2 and MMP 9) to convert into active forms,but also increase dramatically the tissue inhibitor of metalloproteinase(TIMP 1) mRNA contents and reverse the imbalance of MMPs and TIMPs.However,expressions of MMP 2 and MMP 9 were not significantly affected.Suppression of MMP activation and increase of TIMP 1 expression will decrease matrix degradation by MMPs,and consequently inhibit invasions of the cells.These results emphasized the existence of the imbalance between MMPs and TIMPs in tumor invasion and metastasis formation.The value of genistein as a drug for antiinvasion and anti metastasis chemotherapy was suggested.
