Effects of Sex and 17 β-Estradiol on Cardiac Fibroblast Morphology and Signaling Activities In Vitro.

Effects of Sex and 17 β-Estradiol on Cardiac Fibroblast Morphology and Signaling Activities In Vitro.
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性别和 17 β-雌二醇对体外心脏成纤维细胞形态和信号活动的影响。

DOI:
10.3390/cells10102564
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发表时间:
2021-09-28
期刊:
影响因子:
6
通讯作者:
Richardson WJ
Richardson WJ
中科院分区:
生物学2区
文献类型:
--
作者:
Watts K;Richardson WJ

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一些研究已经证明雌激素在减少心脏成纤维细胞(CF)的纤维化反应中的心脏保护能力。然而,大多数这些研究不是性别特异性的,并且那些在细胞水平上利用组织培养塑料,一种比生理条件具有更高刚度的基质。了解男性和女性CF之间的内在差异,在生理上更“健康”的条件下,将有助于阐明其复杂的信号网络的分歧。我们的目的是通过对在8 kPa刚性板上培养的CF中细胞形态和促纤维化信号蛋白的相对水平的变化进行性别分类分析来实现这一点,所述8 kPa刚性板具有和不具有17 β-雌二醇(E2)。循环免疫荧光分析表明,有一个可以忽略不计的变化,由于性别和E2治疗的细胞形态和男性和女性的CF之间的差异发生在生化水平,而不是结构水平。对应于促纤维化活性的几种蛋白质在有和没有E2处理的情况下具有各种性别特异性反应。单细胞相关性分析显示,在不同的实验条件下,蛋白质-蛋白质相互作用。这些发现表明,需要进一步研究男性和女性CF的二态性,以开发更好的定制性心脏纤维化预防和治疗干预措施。
Several studies have demonstrated estrogen’s cardioprotective abilities in decreasing the fibrotic response of cardiac fibroblasts (CFs). However, the majority of these studies are not sex-specific, and those at the cellular level utilize tissue culture plastic, a substrate with a much higher stiffness than physiological conditions. Understanding the intrinsic differences between male and female CFs under more physiologically “healthy” conditions will help to elucidate the divergences in their complex signaling networks. We aimed to do this by conducting a sex-disaggregated analysis of changes in cellular morphology and relative levels of profibrotic signaling proteins in CFs cultured on 8 kPa stiffness plates with and without 17 β-estradiol (E2). Cyclic immunofluorescent analysis indicated that there was a negligible change in cellular morphology due to sex and E2 treatment and that the differences between male and female CFs occur at a biochemical rather than structural level. Several proteins corresponding to profibrotic activity had various sex-specific responses with and without E2 treatment. Single-cell correlation analysis exhibited varied protein–protein interaction across experimental conditions. These findings demonstrate the need for further research into the dimorphisms of male and female CFs to develop better tailored sex-informed prevention and treatment interventions of cardiac fibrosis.
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