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TFEB-TGIF1 轴调节小鼠心外膜细胞中的 EMT。

The TFEB-TGIF1 axis regulates EMT in mouse epicardial cells.

机构信息

Department of Oncology, University of Torino, Torino, Italy.

Candiolo Cancer Institute-IRCCS-FPO, Candiolo, Italy.

出版信息

Nat Commun. 2022 Sep 3;13(1):5191. doi: 10.1038/s41467-022-32855-3.

DOI:10.1038/s41467-022-32855-3
PMID:36057632
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9440911/
Abstract

Epithelial-mesenchymal transition (EMT) is a complex and pivotal process involved in organogenesis and is related to several pathological processes, including cancer and fibrosis. During heart development, EMT mediates the conversion of epicardial cells into vascular smooth muscle cells and cardiac interstitial fibroblasts. Here, we show that the oncogenic transcription factor EB (TFEB) is a key regulator of EMT in epicardial cells and that its genetic overexpression in mouse epicardium is lethal due to heart defects linked to impaired EMT. TFEB specifically orchestrates the EMT-promoting function of transforming growth factor (TGF) β, and this effect results from activated transcription of thymine-guanine-interacting factor (TGIF)1, a TGFβ/Smad pathway repressor. The Tgif1 promoter is activated by TFEB, and in vitro and in vivo findings demonstrate its increased expression when Tfeb is overexpressed. Furthermore, Tfeb overexpression in vitro prevents TGFβ-induced EMT, and this effect is abolished by Tgif1 silencing. Tfeb loss of function, similar to that of Tgif1, sensitizes cells to TGFβ, inducing an EMT response to low doses of TGFβ. Together, our findings reveal an unexpected function of TFEB in regulating EMT, which might provide insights into injured heart repair and control of cancer progression.

摘要

上皮-间充质转化 (EMT) 是一个复杂而关键的过程，涉及器官发生，并与包括癌症和纤维化在内的几种病理过程有关。在心脏发育过程中，EMT 介导心外膜细胞向血管平滑肌细胞和心脏间质成纤维细胞的转化。在这里，我们表明致癌转录因子 EB (TFEB) 是心外膜细胞 EMT 的关键调节因子，其在小鼠心外膜中的遗传过表达由于与 EMT 受损相关的心脏缺陷而致命。TFEB 特异性协调 TGFβ 的 EMT 促进功能，这种效应是由于胸腺嘧啶-鸟嘌呤相互作用因子 (TGIF)1 的转录激活，TGIF1 是 TGFβ/Smad 途径的抑制剂。Tgif1 启动子被 TFEB 激活，并且体外和体内研究结果表明，当 Tfeb 过表达时，其表达增加。此外，Tfeb 在体外过表达可防止 TGFβ 诱导的 EMT，而 Tgif1 沉默则消除了这种效应。Tfeb 功能丧失，类似于 Tgif1，使细胞对 TGFβ 敏感，导致低剂量 TGFβ 诱导 EMT 反应。总之，我们的研究结果揭示了 TFEB 在调节 EMT 中的一个意想不到的功能，这可能为受损心脏修复和癌症进展的控制提供新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a75/9440911/f93b4fb69706/41467_2022_32855_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a75/9440911/6a070175810a/41467_2022_32855_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a75/9440911/f447c107e972/41467_2022_32855_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a75/9440911/56fa4e1ae10d/41467_2022_32855_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a75/9440911/007320008dcf/41467_2022_32855_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a75/9440911/0d8a854959c1/41467_2022_32855_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a75/9440911/e74401bb75dd/41467_2022_32855_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a75/9440911/978b0756d662/41467_2022_32855_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a75/9440911/a2059253a73e/41467_2022_32855_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a75/9440911/f93b4fb69706/41467_2022_32855_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a75/9440911/6a070175810a/41467_2022_32855_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a75/9440911/f447c107e972/41467_2022_32855_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a75/9440911/56fa4e1ae10d/41467_2022_32855_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a75/9440911/007320008dcf/41467_2022_32855_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a75/9440911/0d8a854959c1/41467_2022_32855_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a75/9440911/e74401bb75dd/41467_2022_32855_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a75/9440911/978b0756d662/41467_2022_32855_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a75/9440911/a2059253a73e/41467_2022_32855_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a75/9440911/f93b4fb69706/41467_2022_32855_Fig9_HTML.jpg

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2
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Mol Oncol. 2021 Feb;15(2):327-346. doi: 10.1002/1878-0261.12867. Epub 2020 Dec 23.
3
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Nat Commun. 2025 Feb 21;16(1):1865. doi: 10.1038/s41467-025-56922-7.
4
LncRNAs in the Domain Are Essential for Mid-Embryonic Heart Development.领域中的 lncRNAs 对胚胎中期心脏发育至关重要。
Int J Mol Sci. 2024 Jul 26;25(15):8184. doi: 10.3390/ijms25158184.
5
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6
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7
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8
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5
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9
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10
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