The cooperative interplay among inflammation, necroptosis and YAP pathway contributes to the folate deficiency-induced liver cells enlargement

Wan Yu Chi, Tsun Hsien Hsiao, Gang Hui Lee, I. Hsiu Su, Bing Hung Chen, Ming Jer Tang, Tzu Fun Fu

研究成果: Article同行評審

摘要

Change in cell size may bring in profound impact to cell function and survival, hence the integrity of the organs consisting of those cells. Nevertheless, how cell size is regulated remains incompletely understood. We used the fluorescent zebrafish transgenic line Tg-GGH/LR that displays inducible folate deficiency (FD) and hepatomegaly upon FD induction as in vivo model. We found that FD caused hepatocytes enlargement and increased liver stiffness, which could not be prevented by nucleotides supplementations. Both in vitro and in vivo studies indicated that RIPK3/MLKL-dependent necroptotic pathway and Hippo signaling interactively participated in this FD-induced hepatocytic enlargement in a dual chronological and cooperative manner. FD also induced hepatic inflammation, which convenes a dialog of positive feedback loop between necroptotic and Hippo pathways. The increased MMP13 expression in response to FD elevated TNFα level and further aggravated the hepatocyte enlargement. Meanwhile, F-actin was circumferentially re-allocated at the edge under cell membrane in response to FD. Our results substantiate the interplay among intracellular folate status, pathways regulation, inflammatory responses, actin cytoskeleton and cell volume control, which can be best observed with in vivo platform. Our data also support the use of this Tg-GGH/LR transgenic line for the mechanistical and therapeutic research for the pathologic conditions related to cell size alteration.

原文English
文章編號397
期刊Cellular and Molecular Life Sciences
79
發行號8
DOIs
出版狀態Published - 2022 8月

All Science Journal Classification (ASJC) codes

  • 分子醫學
  • 分子生物學
  • 藥理
  • 細胞與分子神經科學
  • 細胞生物學

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