Physiological and pathological roles of the Hippo‐YAP/TAZ signaling pathway in liver formation, homeostasis, and tumorigenesis DOI Creative Commons
Hiroshi Nishina

Cancer Science, Journal Year: 2022, Volume and Issue: 113(6), P. 1900 - 1908

Published: March 29, 2022

Abstract The liver plays central homeostatic roles in metabolism and detoxification, has a remarkable capacity to fully recover from injuries caused by the various insults which it is constantly exposed. To fulfill these functions, must maintain specific size so regulate its cell numbers. It also remove senescent, transformed, and/or injured cells that impair function can lead diseases such as cirrhosis cancer. Despite their importance, however, mechanisms governing control homeostasis have resisted delineation. discovery of Hippo intracellular signaling pathway downstream effectors, transcriptional coactivators Yes‐associated protein (YAP) coactivator with PDZ‐binding motif (TAZ), provided partial elucidation mechanisms. Hippo‐YAP/TAZ considered be cell’s sensor immediate microenvironment surround it, this responds changes elements ECM, cell–cell tension, adhesion. Once triggered, negatively regulates binding YAP/TAZ transcription factors TEAD Smad, controlling ability drive gene expression needed for cellular responses proliferation, survival, stemness. Numerous KO mouse strains lacking YAP/TAZ, well transgenic mice showing hyperactivation, been generated, effects mutations on development, size, regeneration, homeostasis, tumorigenesis reported. In review, I summarize components regulation signaling, discuss context physiology pathology.

Language: Английский

The Hippo signalling pathway and its implications in human health and diseases DOI Creative Commons

Minyang Fu,

Yuan Hu,

Tianxia Lan

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: Nov. 8, 2022

Abstract As an evolutionarily conserved signalling network, the Hippo pathway plays a crucial role in regulation of numerous biological processes. Thus, substantial efforts have been made to understand upstream signals that influence activity pathway, as well its physiological functions, such cell proliferation and differentiation, organ growth, embryogenesis, tissue regeneration/wound healing. However, dysregulation can cause variety diseases, including cancer, eye cardiac pulmonary renal hepatic immune dysfunction. Therefore, therapeutic strategies target dysregulated components might be promising approaches for treatment wide spectrum diseases. Here, we review key critical functions controlled by pathway. Additionally, diseases associated with alterations potential therapies targeting will discussed.

Language: Английский

Citations

347
Mechanical regulation of chromatin and transcription DOI
Sirio Dupont, Sara A. Wickström

Nature Reviews Genetics, Journal Year: 2022, Volume and Issue: 23(10), P. 624 - 643

Published: May 23, 2022

Language: Английский

Citations

148
Control of stem cell renewal and fate by YAP and TAZ DOI
Jordan H. Driskill, Duojia Pan

Nature Reviews Molecular Cell Biology, Journal Year: 2023, Volume and Issue: 24(12), P. 895 - 911

Published: Aug. 25, 2023

Language: Английский

Citations

74
Molecular mechanisms in liver repair and regeneration: from physiology to therapeutics DOI Creative Commons
Xiao Ma, Tengda Huang, Xi Chen

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: Feb. 8, 2025

Language: Английский

Citations

7
ROS-induced cytosolic release of mitochondrial PGAM5 promotes colorectal cancer progression by interacting with MST3 DOI Creative Commons
Shiyang Wang, Xi Wu,

Wenxin Bi

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 6, 2025

Aberrant release of mitochondrial reactive oxygen species (mtROS) in response to cellular stress is well known for promoting cancer progression. However, precise molecular mechanism by which mtROS contribute epithelial progression remains only partially understood. Here, using colorectal (CRC) models, we show that upon sensing excessive mtROS, phosphatase PGAM5, normally localizes the mitochondria, undergoes aberrant cleavage presenilin-associated rhomboid-like protein (PARL), becoming released into cytoplasm. Cytosolic PGAM5 then directly binds and dephosphorylates MST3 kinase. This, turn, prevents STK25-mediated LATS1/2 phosphorylation, leading YAP activation CRC Importantly, depletion reciprocally promotes accumulation cytosolic inducing damage. Taken together, these findings demonstrate how activating via a post-transcriptional positive feedback loop between MST3, both can serve as potential targets developing next-generation anti-colon therapeutics. Dysregulation contributes intestinal tumorigenesis. Here authors report induces cytoplasm subsequent dephosphorylation kinase,

Language: Английский

Citations

4
Decellularized extracellular matrix mediates tissue construction and regeneration DOI Creative Commons
Chuanqi Liu, Ming Pei, Qingfeng Li

et al.

Frontiers of Medicine, Journal Year: 2021, Volume and Issue: 16(1), P. 56 - 82

Published: Dec. 28, 2021

Contributing to organ formation and tissue regeneration, extracellular matrix (ECM) constituents provide with three-dimensional (3D) structural integrity cellular-function regulation. Containing the crucial traits of cellular microenvironment, ECM substitutes mediate cell-matrix interactions prompt stem-cell proliferation differentiation for 3D organoid construction in vitro or regeneration vivo. However, these ECMs are often applied generically have yet be extensively developed specific cell types cultures. Cultured cells also produce rich ECM, particularly stromal cells. Cellular improves culture development remodeling during wound healing after implantation into host as well. Gaining better insight derived from either that regulate reconstruction helps us select, produce, implant most suitable thus promote vivo regeneration. Overall, decellularization methodologies tissue/cell-derived scaffolds cellular-growth supplements used propagation discussed. Moreover, current preclinical applications by which components modulate wound-healing process reviewed.

Language: Английский

Citations

94
Stem cell therapy in liver regeneration: Focus on mesenchymal stem cells and induced pluripotent stem cells DOI
Lu Zhang,

Xiao-Jing-Nan Ma,

Yuan-Yuan Fei

et al.

Pharmacology & Therapeutics, Journal Year: 2021, Volume and Issue: 232, P. 108004 - 108004

Published: Sept. 28, 2021

Language: Английский

Citations

66
Extra- and Intra-Cellular Mechanisms of Hepatic Stellate Cell Activation DOI Creative Commons
Yufei Yan,

Jiefei Zeng,

Linhao Xing

et al.

Biomedicines, Journal Year: 2021, Volume and Issue: 9(8), P. 1014 - 1014

Published: Aug. 14, 2021

Hepatic fibrosis is characterized by the pathological accumulation of extracellular matrix (ECM) in liver resulting from persistent injury and wound-healing reaction induced various insults. Although hepatic considered reversible after eliminating cause injury, chronic left unchecked can progress to cirrhosis cancer. A better understanding cellular molecular mechanisms controlling fibrotic response needed develop novel clinical strategies. It well documented that activated stellate cells (HSCs) most principal players promoting synthesis deposition ECM components. In current review, we discuss pathways HSC activation, emphasizing emerging extra- intra-cellular signals drive this important fibrosis. number cell types external stimuli converge upon HSCs promote their including hepatocytes, sinusoidal endothelial cells, macrophages, cytokines, altered ECM, hepatitis viral infection, enteric dysbiosis, lipid metabolism disorder, exosomes, microRNAs, alcohol, drugs parasites. We also signaling intracellular events individually or synergistically TGFβ/Smad, Notch, Wnt/β-catenin, Hedgehog Hippo pathways. These findings will provide potential therapeutic targets arrest reverse cirrhosis.

Language: Английский

Citations

64
Hippo signaling pathway and respiratory diseases DOI Creative Commons
Weifeng Tang, Min Li,

Xiaoting Yangzhong

et al.

Cell Death Discovery, Journal Year: 2022, Volume and Issue: 8(1)

Published: April 20, 2022

The hippo signaling pathway is a highly conserved evolutionary that plays an important role in regulating cell proliferation, organ size, tissue development, and regeneration. Increasing evidences consider the involved process of respiratory diseases. Hippo mainly composed mammalian STE20-like kinase 1/2 (MST1/2), large tumor suppressor (LATS1/2), WW domain Sav family containing protein 1 (SAV1), MOB activator (MOB1), Yes-associated (YAP) or transcriptional coactivator with PDZ-binding motif (TAZ), members TEA (TEAD) family. YAP cascade effector pathway. activation promotes pulmonary arterial vascular smooth muscle cells (PAVSMCs) which leads to remodeling; thereby hypertension (PAH) aggravated. While loss high expression inflammatory genes accumulation cells, pneumonia consequently exacerbated. In addition, overexpressed proliferation lung fibroblasts collagen deposition; idiopathic fibrosis (IPF) promoted. Moreover, knockout reduces deposition senescence adult alveolar epithelial (AECs); hence IPF slowed. may be repair acute injury (ALI) by promoting differentiation progenitor intervening capillary endothelium. asthma. conclusion, More researches are needed focus on molecular mechanisms participates

Language: Английский

Citations

45
The m6A methyltransferase Mettl3 deficiency attenuates hepatic stellate cell activation and liver fibrosis DOI Creative Commons

Yanli Li,

Xinmei Kang, Zhuowei Zhou

et al.

Molecular Therapy, Journal Year: 2022, Volume and Issue: 30(12), P. 3714 - 3728

Published: Aug. 3, 2022

Activation of hepatic stellate cells (HSCs) is a central driver liver fibrosis. Previous investigations have identified various altered epigenetic landscapes during the cellular progression HSC activation. N6-methyladenosine (m6A) most abundant internal RNA modification in eukaryotic and dynamically regulated under physiological pathophysiological conditions. However, functional role Mettl3-mediated m6A fibrosis remains elusive. Here, we found that HSC-specific knockout methyltransferase Mettl3 suppressed activation significantly alleviated Multi-omics analysis HSCs showed depletion reduced deposition on mRNA transcripts Lats2 (a player Hippo/YAP signaling pathway) slowed down their degradation. Elevated increased phosphorylation downstream transcription factor YAP, YAP nuclear translocation, decreased pro-fibrotic gene expression. Overexpressing mutant resistant to by partially rescued expression Mettl3-deficient HSCs. Our study revealed disruption mitigated controlling pathway, providing potential therapeutic strategies alleviate targeting epitranscriptomic machinery.

Language: Английский

Citations

43