Matrix metalloproteinase inhibition influences aspects of photoperiod stimulated ovarian recrudescence in Siberian hamsters.
Matrix metalloproteinase inhibition influences aspects of photoperiod stimulated ovarian recrudescence in Siberian hamsters.
复制标题
DOI：
10.1016/j.ygcen.2015.04.010
复制
发表时间：
2015-05-15
影响因子：
2.7
通讯作者：
Young, Kelly A.
中科院分区：
文献类型：
--
作者：
Shahed, Asha;Simmons, Jamie J.;Featherstone, Sydney L.;Young, Kelly A.
用抑制剂GM 6001阻断体内基质金属蛋白酶（MMP）活性可阻止光退化西伯利亚仓鼠光刺激卵巢复发。由于基质金属蛋白酶的直接和间接作用影响了卵巢的多种功能，我们研究了复发期间体内基质金属蛋白酶抑制剂对卵巢类固醇生成急性调节蛋白（星星）、3β-羟基类固醇脱氢酶（3β-HSD）、Cyp 19 a1芳香化酶、表皮生长因子受体（EGFR）、双调蛋白（Areg）、雌激素受体（ER）（Esr 1和Esr 2）、MMP的组织抑制剂（TIMP-1、TIMP-2、TIMP-3）、增殖细胞核抗原（PCNA）、血管内皮生长因子A（VEGFA）、其受体VEGFR-2和血管生成素-2（Ang-2）。雌性西伯利亚仓鼠被随机分配到四个光周期组之一：刺激性长（LD）或抑制性短（SD）光周期，或从SD转移到LD 2周（转移后，PT）。一半的PT仓鼠每天注射（ip）GM 6001（PTG）。SD暴露降低了PT组卵巢星星、3β-HSD、Cyp 19 a1、Esr 1、Esr 2、TIMPs 2-3、PCNA、VEGFR-2和Ang-2的mRNA表达（p < 0.05），光刺激2周恢复了PT组卵巢3β-HSD和PCNA的mRNA表达，并增加了Areg和VEGFA的mRNA表达。与光刺激（PT）相比，GM 6001处理可增加TIMP-1、TIMP-2和TIMP-3以及PCNA mRNA的表达，但抑制Areg mRNA的表达。光周期和GM 6001均不改变EGFR表达。该研究的结果表明，GM 6001对MMP活性的体内抑制可能以两种方式阻碍卵巢复发，特别是卵泡生长：（1）直接通过部分抑制EGFR配体如Areg的释放，从而潜在地影响EGFR活化及其下游途径，和（2）间接通过其对TIMP的作用，TIMP本身可以影响增殖、血管生成和卵泡生长。
Blocking matrix metalloproteinase (MMP) activity in vivo with inhibitor GM6001 impedes photostimulated ovarian recrudescence in photoregressed Siberian hamsters. Since direct and indirect effects of MMPs influence a myriad of ovarian functions, we investigated the effect of in vivo MMP inhibition during recrudescence on ovarian mRNA expression of steroidogenic acute regulatory protein (StAR), 3β-hy-droxysteroid dehydrogenase (3β-HSD), Cyp19a1 aromatase, epidermal growth factor receptor (EGFR), amphiregulin (Areg), estrogen receptors (Esr1 and Esr2), tissue inhibitors of MMPs (TIMP-1,-2,-3), proliferating cell nuclear antigen (PCNA), vascular endothelial growth factor A (VEGFA), its receptor VEGFR-2, and angiopoietin-2 (Ang-2). Female Siberian hamsters were randomly assigned to one of four photoperiod groups: stimulatory long (LD) or inhibitory short (SD) photoperiods, or transferred from SD to LD for 2 weeks (post-transfer, PT). Half of the PT hamsters were injected (ip) daily with GM6001 (PTG). SD exposure reduced ovarian StAR, 3β-HSD, Cyp19a1, Esr1, Esr2, TIMPs 2–3, PCNA, VEGFR-2 and Ang-2 mRNA expression (p < 0.05), and 2 weeks of photostimulation restored mRNA expression of 3β-HSD and PCNA and increased Areg and VEGFA mRNA expression in the PT group. GM6001 treatment during photostimulation (PTG) increased TIMP-1, -2 and -3 and PCNA mRNA, but inhibited Areg mRNA expression compared to PT. Neither photoperiod nor GM6001 altered EGFR expression. Results of this study suggest that in vivo inhibition of MMP activity by GM6001 may impede ovarian recrudescence, particularly follicular growth, in two ways: (1) directly by partially inhibiting the release of EGFR ligands like Areg, thereby potentially affecting EGFR activation and its downstream pathway, and (2) indirectly by its effect on TIMPs which themselves can affect proliferation, angiogenesis and follicular growth.
登录
查看更多内容
影响因子：
--
作者：
Panigone, Sara;Hsieh, Minnie;Conti, Marco
通讯作者：
Conti, Marco
影响因子：
5.6
作者：
JOHNSON, MD;KIM, HRC;POLVERINI, PJ
通讯作者：
POLVERINI, PJ
影响因子：
4.8
作者：
GOLDENBERG, RL;ROSS, GT;VAITUKAITIS, JL
通讯作者：
VAITUKAITIS, JL
影响因子：
--
作者：
Carbajal, Liliana;Biswas, Anindita;Hammes, Stephen R.
通讯作者：
Hammes, Stephen R.
DOI：
10.1016/j.cbpa.2009.10.024
发表时间：
2010-01-01
影响因子：
2.3
作者：
Phalen, Adrien N.;Wexler, Ron;Place, Ned J.
通讯作者：
Place, Ned J.