Deletion of low molecular weight protein tyrosine phosphatase (Acp1) protects against stress-induced cardiomyopathy.
Deletion of low molecular weight protein tyrosine phosphatase (Acp1) protects against stress-induced cardiomyopathy.
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DOI：
10.1002/path.4594
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发表时间：
2015-12
影响因子：
7.3
通讯作者：
Poizat, Coralie
中科院分区：
文献类型：
--
作者：
Wade, Fallou;Quijada, Pearl;Al-Haffar, Kamar Mohamed Adib;Awad, Salma Mahmoud;Kunhi, Muhammad;Toko, Haruhiro;Marashly, Qussay;Belhaj, Karim;Zahid, Israa;Al-Mohanna, Falah;Stanford, Stephanie M.;Alvarez, Roberto;Liu, Yingge;Colak, Dilek;Jordan, Maria C.;Roos, Kenneth P.;Assiri, Abdullah;Al-Habeeb, Waleed;Sussman, Mark;Bottini, Nunzio;Poizat, Coralie
关键词：
由 ACP1 基因编码的低分子量蛋白酪氨酸磷酸酶 (LMPTP) 是一种普遍表达的磷酸酶，其在心脏和心脏病中的体内功能仍不清楚。为了研究 LMPTP 在心脏功能中的体内作用，我们培育了 Acp1 基因座基因失活的小鼠，并研究了它们对长期压力超负荷的反应。 Acp1−/− 小鼠发育正常，衰老小鼠在基础条件下主要组织未表现出病理变化。然而，Acp1−/− 小鼠对压力超负荷肥大和心力衰竭具有惊人的抵抗力。 Lmptp 在胚胎小鼠心脏中表达较高，在出生后阶段下降，在成年小鼠衰竭心脏中表达增加。我们还表明，LMPTP 表达在人类终末期心力衰竭中增加。与它们的受保护表型一致，承受压力超负荷肥大的 Acp1−/− 小鼠的纤维化减弱，纤维化基因的表达减少。转录谱和分子信号分析表明，Acp1−/− 小鼠对病理性心脏应激的抵抗力与胎儿心脏基因的边缘重新表达、胰岛素受体 β 磷酸化增加、PKA 和肝配蛋白受体表达以及 CaMKIIδ 通路失活相关。我们的数据表明，Lmptp 的消融可抑制病理性心脏重塑，并表明 LMPTP 的抑制可能对人类心力衰竭的治疗具有治疗意义。 © 2015 作者。 《病理学杂志》由 John Wiley & Sons Ltd 代表大不列颠及爱尔兰病理学会出版。
The low molecular weight protein tyrosine phosphatase (LMPTP), encoded by the ACP1 gene, is a ubiquitously expressed phosphatase whose in vivo function in the heart and in cardiac diseases remains unknown. To investigate the in vivo role of LMPTP in cardiac function, we generated mice with genetic inactivation of the Acp1 locus and studied their response to long‐term pressure overload. Acp1−/− mice develop normally and ageing mice do not show pathology in major tissues under basal conditions. However, Acp1−/− mice are strikingly resistant to pressure overload hypertrophy and heart failure. Lmptp expression is high in the embryonic mouse heart, decreased in the postnatal stage, and increased in the adult mouse failing heart. We also show that LMPTP expression increases in end‐stage heart failure in humans. Consistent with their protected phenotype, Acp1−/− mice subjected to pressure overload hypertrophy have attenuated fibrosis and decreased expression of fibrotic genes. Transcriptional profiling and analysis of molecular signalling show that the resistance of Acp1−/− mice to pathological cardiac stress correlates with marginal re‐expression of fetal cardiac genes, increased insulin receptor beta phosphorylation, as well as PKA and ephrin receptor expression, and inactivation of the CaMKIIδ pathway. Our data show that ablation of Lmptp inhibits pathological cardiac remodelling and suggest that inhibition of LMPTP may be of therapeutic relevance for the treatment of human heart failure. © 2015 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
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DOI：
10.1073/pnas.011404098
发表时间：
2001-01-02
影响因子：
11.1
作者：
Li, C;Wong, WH
通讯作者：
Wong, WH
影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J
DOI：
10.1073/pnas.94.15.8121
发表时间：
1997-07-22
影响因子：
11.1
作者：
DAngelo, DD;Sakata, Y;Dorn, GW
通讯作者：
Dorn, GW
影响因子：
5
作者：
Gomez, Elodie;Vercauteren, Magali;Richard, Vincent
通讯作者：
Richard, Vincent
影响因子：
5.5
作者：
Dries, Jessica L.;Kent, Susan D.;Virag, Jitka A. I.
通讯作者：
Virag, Jitka A. I.