HSPA12A Stimulates p38/ERK-AP-1 Signaling to Promote Angiogenesis and Is Required for Functional Recovery Postmyocardial Infarction.
HSPA12A Stimulates p38/ERK-AP-1 Signaling to Promote Angiogenesis and Is Required for Functional Recovery Postmyocardial Infarction.
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DOI：
10.1155/2022/2333848
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发表时间：
2022
影响因子：
--
通讯作者：
Liu, Li
中科院分区：
文献类型：
--
作者：
Li, Tingting;Wu, Jun;Yu, Wansu;Mao, Qian;Cheng, Hao;Zhang, Xiaojin;Li, Yuehua;Li, Chuanfu;Ding, Zhengnian;Liu, Li
血管生成在心肌梗死（MI）后伤口愈合中起着关键作用。然而，目前临床上仍缺乏理想的血管生成治疗方法来挽救缺血性心脏，这表明对血管生成调控的更多认识是迫切需要的。热休克蛋白A12 A（HSPA 12 A）是HSP 70家族的一个非典型成员。在这里，我们证明了HSPA 12 A在内皮管形成过程中上调，这是体外血管生成的特征。有趣的是，HSPA 12 A的过表达促进了体外血管生成特性，包括内皮细胞的增殖、迁移和管形成。相比之下，HSPA 12 A的缺陷损害心肌血管生成和恶化心肌梗死后的心功能不全小鼠。与血管生成相关的基因（VEGF、VEGFR 2和Ang-1）的表达在小鼠MI心脏中因HSPA 12 A缺乏而降低，而在内皮细胞中因HSPA 12 A过表达而增加。HSPA 12 A在内皮细胞中的过表达增加了AP-1的磷酸化水平和核定位，AP-1是一种主导血管生成基因表达的转录因子。此外，HSPA 12 A增加p38和ERK磷酸化水平，而抑制p38或ERK减少了HSPA 12 A促进的AP-1磷酸化和核定位，以及VEGF和VEGFR 2在内皮细胞中的表达。值得注意的是，抑制p38或ERK减弱了HSPA 12 A促进的体外血管生成特征。这些发现将HSPA 12 A确定为一种新的血管生成激活剂，HSPA 12 A可能代表缺血性心脏病患者心肌愈合管理的可行策略。
Angiogenesis plays a critical role in wound healing postmyocardial infarction (MI). However, there is still a lack of ideal angiogenic therapeutics for rescuing ischemic hearts clinically, suggesting that a more understanding regarding angiogenesis regulation is urgently needed. Heat shock protein A12A (HSPA12A) is an atypical member of the HSP70 family. Here, we demonstrated that HSPA12A was upregulated during endothelial tube formation, a characteristic of in vitro angiogenesis. Intriguingly, overexpression of HSPA12A promoted in vitro angiogenic characteristics including proliferation, migration, and tube formation of endothelial cells. By contrast, deficiency of HSPA12A impaired myocardial angiogenesis and worsened cardiac dysfunction post-MI in mice. The expression of genes related to angiogenesis (VEGF, VEGFR2, and Ang-1) was decreased by HSPA12A deficiency in MI hearts of mice, whereas their expression was increased by HSPA12A overexpression in endothelial cells. HSPA12A overexpression in endothelial cells increased phosphorylation levels and nuclear localization of AP-1, a transcription factor dominating angiogenic gene expression. Also, HSPA12A increased p38 and ERK phosphorylation levels, whereas inhibition of p38 or ERKs diminished the HSPA12A-promoted AP-1 phosphorylation and nuclear localization, as well as VEGF and VEGFR2 expression in endothelial cells. Notably, inhibition of either p38 or ERKs diminished the HSPA12A-promoted in vitro angiogenesis characteristics. The findings identified HSPA12A as a novel angiogenesis activator, and HSPA12A might represent a viable strategy for the management of myocardial healing in patients with ischemic heart diseases.
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影响因子：
9.8
作者：
Gianni-Barrera R;Butschkau A;Uccelli A;Certelli A;Valente P;Bartolomeo M;Groppa E;Burger MG;Hlushchuk R;Heberer M;Schaefer DJ;Gürke L;Djonov V;Vollmar B;Banfi A
通讯作者：
Banfi A
DOI：
10.1016/j.omtm.2020.05.030
发表时间：
2020-09-11
影响因子：
4.7
作者：
Anttila, Vesa;Saraste, Antti;Gan, Li-Ming
通讯作者：
Gan, Li-Ming
DOI：
10.1073/pnas.1805683115
发表时间：
2018-06-12
影响因子：
11.1
作者：
Henriques, Ana;Koliaraki, Vasiliki;Kollias, George
通讯作者：
Kollias, George
影响因子：
3.8
作者：
Rashmi, K. C.;Atreya, H. S.;Aparna, H. S.
通讯作者：
Aparna, H. S.
热休克蛋白 12A 是一种新型 PCNA 结合蛋白，可促进肝细胞癌生长
影响因子：
5.4
作者：
Cheng, Hao;Cao, Xiaofei;Ding, Zhengnian
通讯作者：
Ding, Zhengnian