当前位置: X-MOL 学术BBA Mol. Cell Res. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Role of FoxO3a as a negative regulator of the cardiac myofibroblast conversion induced by TGF-β1.
Biochimica et Biophysica Acta (BBA) - Molecular Cell Research ( IF 4.6 ) Pub Date : 2020-03-10 , DOI: 10.1016/j.bbamcr.2020.118695
Raúl Vivar 1 , Claudio Humeres 1 , Renatto Anfossi 2 , Samir Bolivar 2 , Mabel Catalán 1 , Joseph Hill 3 , Sergio Lavandero 4 , Guillermo Diaz-Araya 5
Affiliation  

Cardiac fibroblasts (CFs) are necessary to maintain extracellular matrix (ECM) homeostasis in the heart. Normally, CFs are quiescent and secrete small amounts of ECM components, whereas, in pathological conditions, they differentiate into more active cells called cardiac myofibroblasts (CMF). CMF conversion is characteristic of cardiac fibrotic diseases, such as heart failure and diabetic cardiomyopathy. TGF-β1 is a key protein involved in CMF conversion. SMADs are nuclear factor proteins activated by TGF-β1 that need other proteins, such as forkhead box type O (FoxO) family members, to promote CMF conversion. FoxO1, a member of this family protein, is necessary for TGF-β1-induced CMF conversion, whereas the role of FoxO3a, another FoxO family member, is unknown. FoxO3a plays an important role in many fibrotic processes in the kidney and lung. However, the participation of FoxO3a in the conversion of CFs into CMF is not clear. In this paper, we demonstrate that TGF-β1 decreases the activation and expression of FoxO3a in CFs. FoxO3a regulation by TGF-β1 requires activated SMAD3, ERK1/2 and Akt. Furthermore, we show that FoxO1 is crucial in the FoxO3a regulation induced by TGF-β1, as shown by overexpressed FoxO1 enhancing and silenced FoxO1 suppressing the effects of TGF-β1 on FoxO3a. Finally, the regulation of TGF-β1-induced CMF conversion was enhanced by FoxO3a silencing and suppressed by inhibited FoxO3a degradation. Considering these collective findings, we suggest that FoxO3a acts as a negative regulator of the CMF conversion that is induced by TGF-β1.

中文翻译:

FoxO3a作为TGF-β1诱导的心肌成纤维细胞转化的负调节剂。

心脏成纤维细胞(CFs)是维持心脏内细胞外基质(ECM)动态平衡所必需的。正常情况下,CF处于静止状态并分泌少量ECM成分,而在病理情况下,它们会分化为更多的活性细胞,称为心肌成纤维细胞(CMF)。CMF转换是心脏纤维化疾病(如心力衰竭和糖尿病性心肌病)的特征。TGF-β1是参与CMF转化的关键蛋白。SMAD是被TGF-β1激活的核因子蛋白,需要其他蛋白(例如O型叉头盒(FoxO)家族成员)来促进CMF转化。FoxO1,此家族蛋白的成员,对于TGF-β1诱导的CMF转化是必需的,而另一个FoxO家族成员FoxO3a的作用尚不清楚。FoxO3a在肾和肺的许多纤维化过程中起重要作用。但是,尚不清楚FoxO3a是否参与将CF转化为CMF。在本文中,我们证明了TGF-β1降低了CF中FoxO3a的激活和表达。TGF-β1调节FoxO3a需要激活SMAD3,ERK1 / 2和Akt。此外,我们显示,FoxO1在TGF-β1诱导的FoxO3a调控中至关重要,这由过表达的FoxO1增强和沉默的FoxO1抑​​制TGF-β1对FoxO3a的作用所证实。最后,通过FoxO3a沉默增强了TGF-β1诱导的CMF转化的调控,并通过抑制FoxO3a降解抑制了TGF-β1诱导的CMF转化。考虑到这些集体发现,我们建议FoxO3a充当TGF-β1诱导的CMF转化的负调节剂。我们证明TGF-β1降低了CF中FoxO3a的激活和表达。TGF-β1调节FoxO3a需要激活SMAD3,ERK1 / 2和Akt。此外,我们显示,FoxO1在TGF-β1诱导的FoxO3a调控中至关重要,这由过表达的FoxO1增强和沉默的FoxO1抑​​制TGF-β1对FoxO3a的作用所证实。最后,通过FoxO3a沉默增强了TGF-β1诱导的CMF转化的调控,并通过抑制FoxO3a降解抑制了TGF-β1诱导的CMF转化。考虑到这些集体发现,我们建议FoxO3a充当TGF-β1诱导的CMF转化的负调节剂。我们证明TGF-β1降低了CF中FoxO3a的激活和表达。TGF-β1调节FoxO3a需要激活SMAD3,ERK1 / 2和Akt。此外,我们显示,FoxO1在TGF-β1诱导的FoxO3a调控中至关重要,这由过表达的FoxO1增强和沉默的FoxO1抑​​制TGF-β1对FoxO3a的作用所证实。最后,通过FoxO3a沉默增强了TGF-β1诱导的CMF转化的调控,并通过抑制FoxO3a降解抑制了TGF-β1诱导的CMF转化。考虑到这些集体发现,我们建议FoxO3a充当TGF-β1诱导的CMF转化的负调节剂。如过表达的FoxO1增强和沉默FoxO1抑​​制TGF-β1对FoxO3a的作用所显示。最后,FoxO3a沉默增强了TGF-β1诱导的CMF转化的调控,而抑制的FoxO3a降解则抑制了这种转化。考虑到这些集体发现,我们建议FoxO3a充当TGF-β1诱导的CMF转化的负调节剂。如过表达的FoxO1增强和沉默FoxO1抑​​制TGF-β1对FoxO3a的作用所显示。最后,通过FoxO3a沉默增强了TGF-β1诱导的CMF转化的调控,并通过抑制FoxO3a降解抑制了TGF-β1诱导的CMF转化。考虑到这些集体发现,我们建议FoxO3a充当TGF-β1诱导的CMF转化的负调节剂。
更新日期:2020-03-19
down
wechat
bug