Kanglexin protects against cardiac fibrosis and dysfunction in mice by TGF-β1/ERK1/2 noncanonical pathway.
Kanglexin protects against cardiac fibrosis and dysfunction in mice by TGF-β1/ERK1/2 noncanonical pathway.
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康乐欣通过TGF-β1/ERK1/2非经典途径预防小鼠心脏纤维化和功能障碍
DOI：
10.3389/fphar.2020.572637
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发表时间：
2020
影响因子：
5.6
通讯作者：
Yang B
中科院分区：
文献类型：
--
作者：
Liu X;Han W;An N;Cao N;Wu T;Yang S;Ding L;Chen X;Chen C;Aruhan;Zhang Y;Wang K;Suo L;Huang J;Wang J;Zhao X;Zhu J;Zhang Y;Yang B
心脏纤维化是各种心脏疾病的常见病理表现，抗纤维化治疗是预防心血管系统多种病理过程的有效策略。我们目前报告了一种新的蒽醌化合物（1，8-二羟基-6-甲基-9，10-蒽醌-3-氧乙基琥珀酸酯）命名为康乐新（KLX）的药理学评价，作为一种有效的心脏保护剂，具有抗纤维化活性。我们的研究结果表明，KLX灌胃给药可减轻由横主动脉缩窄（TAC）手术引起的心功能不全、肥大和纤维化。同时，KLX给药减轻了TAC小鼠的内皮向间质转化。在TGF β1处理的原代培养的成年小鼠心脏成纤维细胞（CFs）和人脐静脉内皮细胞（HUVECs）中，KLX抑制细胞增殖和胶原分泌。此外，KLX抑制CF中成纤维细胞向肌成纤维细胞的转化。进一步研究表明，KLX的心脏保护作用可能与抑制TGF-β1/ERK 1/2非经典通路有关。总之，我们的研究表明KLX减轻了TAC小鼠的心脏纤维化和功能障碍，为心脏病理性重塑提供了潜在有效的治疗策略。
Cardiac fibrosis is a common pathological manifestation accompanied by various heart diseases, and antifibrotic therapy is an effective strategy to prevent diverse pathological processes of the cardiovascular system. We currently report the pharmacological evaluation of a novel anthraquinone compound (1,8-dihydroxy-6-methyl-9,10-anthraquinone-3-oxy ethyl succinate) named Kanglexin (KLX), as a potent cardioprotective agent with antifibrosis activity. Our results demonstrated that the administration of KLX by intragastric gavage alleviated cardiac dysfunction, hypertrophy, and fibrosis induced by transverse aortic constriction (TAC) surgical operation. Meanwhile, KLX administration relieved endothelial to mesenchymal transition of TAC mice. In TGF β1-treated primary cultured adult mouse cardiac fibroblasts (CFs) and human umbilical vein endothelial cells (HUVECs), KLX inhibited cell proliferation and collagen secretion. Also, KLX suppressed the transformation of fibroblasts to myofibroblasts in CFs. Further studies revealed that KLX-mediated cardiac protection was due to the inhibitory role of TGF-β1/ERK1/2 noncanonical pathway. In summary, our study indicates that KLX attenuated cardiac fibrosis and dysfunction of TAC mice, providing a potentially effective therapeutic strategy for heart pathological remodeling.
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影响因子：
3.4
作者：
Liu F;Zhang J;Qian J;Wu G;Ma Z
通讯作者：
Ma Z
影响因子：
5
作者：
Maya, Lisandro;Villarreal, Francisco J.
通讯作者：
Villarreal, Francisco J.
影响因子：
2.7
作者：
Massare J;Berry JM;Luo X;Rob F;Johnstone JL;Shelton JM;Bassel-Duby R;Hill JA;Naseem RH
通讯作者：
Naseem RH
影响因子：
7.5
作者：
Lian, Yonggang;Xia, Xiangjun;Zhu, Yunfeng
通讯作者：
Zhu, Yunfeng
影响因子：
5.6
作者：
Fang L;Murphy AJ;Dart AM
通讯作者：
Dart AM