Transforming growth factor β latency: A mechanism of cytokine storage and signalling regulation in liver homeostasis and disease.
Transforming growth factor β latency: A mechanism of cytokine storage and signalling regulation in liver homeostasis and disease.
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转化生长因子β潜伏期：肝稳态和疾病中细胞因子储存和信号调节的机制。
DOI：
10.1016/j.jhepr.2021.100397
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发表时间：
2022-03
期刊：
影响因子：
--
通讯作者：
Dooley S
中科院分区：
文献类型：
--
作者：
Li Y;Fan W;Link F;Wang S;Dooley S
转化生长因子-β（Transforming growth factor-β，TGF-β）是肝脏中的一种有效效应物，其参与了肝损伤后启动的多种过程。TGF-β以高度依赖于环境的方式影响实质、非实质和炎症细胞。其生物利用度对于快速响应各种损伤至关重要。在肝脏中-并且可能在其他器官中-这是通过在细胞外基质中沉积大部分TGF-β作为称为潜伏TGF-β（L-TGF-β）的失活前体形式而实现的。几种基质体蛋白参与基质沉积、潜在复合物稳定和L-TGF-β的活化。细胞外基质蛋白1（ECM 1）最近被鉴定为维持健康肝脏中沉积的L-TGF-β的潜伏期的关键因素。事实上，其消耗引起自发的TGF-β信号传导激活，对肝脏结构和功能具有有害影响。本文综述了目前对细胞内L-TGF-β复合物形成、分泌、基质沉积和活化的认识，并描述了所涉及的蛋白质和过程。此外，我们强调了在肝纤维化和肝癌中减弱L-TGF-β活化的治疗潜力。
Transforming growth factor-β (TGF-β) is a potent effector in the liver, which is involved in a plethora of processes initiated upon liver injury. TGF-β affects parenchymal, non-parenchymal, and inflammatory cells in a highly context-dependent manner. Its bioavailability is critical for a fast response to various insults. In the liver – and probably in other organs – this is made possible by the deposition of a large portion of TGF-β in the extracellular matrix as an inactivated precursor form termed latent TGF-β (L-TGF-β). Several matrisomal proteins participate in matrix deposition, latent complex stabilisation, and activation of L-TGF-β. Extracellular matrix protein 1 (ECM1) was recently identified as a critical factor in maintaining the latency of deposited L-TGF-β in the healthy liver. Indeed, its depletion causes spontaneous TGF-β signalling activation with deleterious effects on liver architecture and function. This review article presents the current knowledge on intracellular L-TGF-β complex formation, secretion, matrix deposition, and activation and describes the proteins and processes involved. Further, we emphasise the therapeutic potential of toning down L-TGF-β activation in liver fibrosis and liver cancer.
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影响因子：
2.9
作者：
ABE, M;HARPEL, JG;RIFKIN, DB
通讯作者：
RIFKIN, DB
影响因子：
8
作者：
通讯作者：
--
DOI：
10.1083/jcb.201308031
发表时间：
2014-05-12
期刊：
The Journal of cell biology
影响因子：
--
作者：
Alcaraz LB;Exposito JY;Chuvin N;Pommier RM;Cluzel C;Martel S;Sentis S;Bartholin L;Lethias C;Valcourt U
通讯作者：
Valcourt U
影响因子：
6.7
作者：
Carlson CM;Turpin EA;Moser LA;O'Brien KB;Cline TD;Jones JC;Tumpey TM;Katz JM;Kelley LA;Gauldie J;Schultz-Cherry S
通讯作者：
Schultz-Cherry S
影响因子：
--
作者：
BarcellosHoff, MH;Dix, TA
通讯作者：
Dix, TA