High throughput interrogation of human liver stellate cells reveals microenvironmental regulation of phenotype.
High throughput interrogation of human liver stellate cells reveals microenvironmental regulation of phenotype.
复制标题
对人肝脏星状细胞的高吞吐量询问揭示了表型的微环境调节。
DOI：
10.1016/j.actbio.2021.11.015
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发表时间：
2022-01-15
影响因子：
9.7
通讯作者：
Underhill GH
中科院分区：
文献类型：
--
作者：
Brougham-Cook A;Jain I;Kukla DA;Masood F;Kimmel H;Ryoo H;Khetani SR;Underhill GH
Liver fibrosis is a common feature of progressive liver disease and is manifested as a dynamic series of alterations in both the biochemical and biophysical properties of the liver. Hepatic stellate cells (HSCs) reside within the perisinusoidal space of the liver sinusoid and are one of the main drivers of liver fibrosis, yet it remains unclear how changes to the sinusoidal microenvironment impact HSC phenotype in the context of liver fibrosis. Cellular microarrays were used to examine and deconstruct the impacts of bio-chemo-mechanical changes on activated HSCs in vitro. Extracellular matrix (ECM) composition and stiffness were found to act individually and in combination to regulate HSC fibrogenic phenotype and proliferation. Hyaluronic acid and collagen III promoted elevated collagen I expression while collagen IV mediated a decrease. Previously activated HSCs exhibited reduced lysyl oxidase (Lox) expression as array substrate stiffness increased, with less dependence on ECM composition. Collagens III and IV increased HSC proliferation, whereas hyaluronic acid had the opposite effect. Meta-analysis performed on these data revealed distinct phenotypic clusters (e.g. low fibrogenesis/high proliferation) as a direct function of their microenvironmental composition. Notably, soft microenvironments mimicking healthy tissue (1 kPa), promoted higher levels of intracellular collagen I and Lox expression in activated HSCs, compared to stiff microenvironments mimicking fibrotic tissue (25 kPa). Collectively, these data suggest potential HSC functional adaptations in response to specific bio-chemo-mechanical changes relevant towards the development of therapeutic interventions. These findings also underscore the importance of the microenvironment when interrogating HSC behavior in healthy, disease, and treatment settings.
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影响因子：
29.4
作者：
Carloni, V;Romanelli, RG;Gentilini, P
通讯作者：
Gentilini, P
影响因子：
4
作者：
Kagan, HM;Li, WD
通讯作者：
Li, WD
细胞外基质组合物的改变指导受损的肝组织的修复。
影响因子：
4.6
作者：
Klaas M;Kangur T;Viil J;Mäemets-Allas K;Minajeva A;Vadi K;Antsov M;Lapidus N;Järvekülg M;Jaks V
通讯作者：
Jaks V
影响因子：
7.7
作者：
Kaylan, Kerim B.;Berg, Ian C.;Underhill, Gregory H.
通讯作者：
Underhill, Gregory H.
DOI：
10.1016/j.diff.2013.07.004
发表时间：
2013-10
期刊：
Differentiation; research in biological diversity
影响因子：
--
作者：
Janmey PA;Wells RG;Assoian RK;McCulloch CA
通讯作者：
McCulloch CA