3D micro-environment regulates NF-κβ dependent adhesion to induce monocyte differentiation.
3D micro-environment regulates NF-κβ dependent adhesion to induce monocyte differentiation.
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DOI：
10.1038/s41419-018-0993-z
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发表时间：
2018-09-11
影响因子：
9
通讯作者：
Sinha DK
中科院分区：
文献类型：
--
作者：
Bhattacharya A;Agarwal M;Mukherjee R;Sen P;Sinha DK
单核细胞的分化需要它们从血液重新定位到组织，因此伴随着物理化学微环境的改变。虽然微环境的生物化学组成诱导分化的机制是已知的，但物理微环境中的类液体到类凝胶的转变还不是很清楚。单核细胞保持非贴壁状态，以防止分化。我们发现，无论化学成分如何，3D凝胶样的微环境都会诱导黏附-丝裂原活化蛋白-核因子-κβ激活的正反馈循环，以促进分化。在2D流体样微环境中，单靠黏附就能通过相同的正反馈信号诱导分化。在流体样微环境中的化学诱导剂处理，通过短暂的p-MAPK脉冲增加单核细胞黏附的倾向。黏附随后诱导分化，确立了黏附在2D/3D微环境中诱导分化的必要条件和充分条件。MAPK和NF-κβ是多个信号通路的关键分子，我们假设生化惰性的三维凝胶样微环境也会影响细胞的其他功能。
Differentiation of monocytes entails their relocation from blood to the tissue, hence accompanied by an altered physicochemical micro-environment. While the mechanism by which the biochemical make-up of the micro-environment induces differentiation is known, the fluid-like to gel-like transition in the physical micro-environment is not well understood. Monocytes maintain non-adherent state to prevent differentiation. We establish that irrespective of the chemical makeup, a 3D gel-like micro-environment induces a positive-feedback loop of adhesion-MAPK-NF-κβ activation to facilitate differentiation. In 2D fluid-like micro-environment, adhesion alone is capable of inducing differentiation via the same positive-feedback signaling. Chemical inducer treatment in fluid-like micro-environment, increases the propensity of monocyte adhesion via a brief pulse of p-MAPK. The adhesion subsequently elicit differentiation, establishing that adhesion is both necessary and sufficient to induce differentiation in 2D/3D micro-environment. MAPK, and NF-κβ being key molecules of multiple signaling pathways, we hypothesize that biochemically inert 3D gel-like micro-environment would also influence other cellular functions.
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影响因子：
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作者：
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DOI：
10.1073/pnas.0712381105
发表时间：
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