N-Acetyl-l-tryptophan inhibits CCl4-induced hepatic fibrogenesis via regulating TGF-β1/SMAD and Hippo/YAP1 signal

Ma, Tingting; Cheng, Huanli; Li, Tongxi; Chen, Yifan; Cai, Tianying; Bai, Junjie; Wu, Ziming; Liang, Tiancheng; Du, Yichao; Fu, Wenguang

doi:10.1016/j.bioorg.2022.105899

Cited by 3 publications

(3 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, through Bulk RNA-Seq and WGCNA analyses, we identified key genes associated with depression pathogenesis and discovered YAP1 as a central molecule. YAP1, a crucial transcriptional co-activator in the Hippo signaling pathway, plays a vital role in regulating cell proliferation, apoptosis, and organ size [30,31]. Recently, increasing evidence suggests that YAP1 also has important functions in the nervous system, including regulating neuronal dendrite development, synaptic plasticity, and neural stem cell proliferation [10,32].…”

Section: Discussionmentioning

confidence: 99%

Single-cell RNA-seq reveals the role of YAP1 in prefrontal cortex microglia in depression

Ma,

Bian,

Jiao

et al. 2024

BMC Neurol

View full text Add to dashboard Cite

Background Depression is a complex mood disorder whose pathogenesis involves multiple cell types and molecular pathways. The prefrontal cortex, as a key brain region for emotional regulation, plays a crucial role in depression. Microglia, as immune cells of the central nervous system, have been closely linked to the development and progression of depression through their dysfunctional states. This study aims to utilize single-cell RNA-seq technology to reveal the pathogenic mechanism of YAP1 in prefrontal cortex microglia in depression. Methods Firstly, we performed cell type identification and differential analysis on normal and depressed prefrontal cortex tissues by mining single-cell RNA-seq datasets from public databases. Focusing on microglia, we conducted sub-clustering, differential gene KEGG enrichment analysis, intercellular interaction analysis, and pseudotime analysis. Additionally, a cross-species analysis was performed to explore the similarities and differences between human and rhesus monkey prefrontal cortex microglia. To validate our findings, we combined bulk RNA-Seq and WGCNA analysis to reveal key genes associated with depression and verified the relationship between YAP1 and depression using clinical samples. Results Our study found significant changes in the proportion and transcriptional profiles of microglia in depressed prefrontal cortex tissues. Further analysis revealed multiple subpopulations of microglia and their associated differential genes and signaling pathways related to depression. YAP1 was identified as a key molecule contributing to the development of depression and was significantly elevated in depression patients. Moreover, the expression level of YAP1 was positively correlated with HAMD scores, suggesting its potential as a biomarker for predicting the onset of depression. Conclusion This study utilized single-cell RNA-seq technology to reveal the pathogenic mechanism of YAP1 in prefrontal cortex microglia in depression, providing a new perspective for a deeper understanding of the pathophysiology of depression and identifying potential targets for developing novel treatment strategies.

show abstract

Section: Discussionmentioning

confidence: 99%

Single-cell RNA-seq reveals the role of YAP1 in prefrontal cortex microglia in depression

Ma,

Bian,

Jiao

et al. 2024

BMC Neurol

View full text Add to dashboard Cite

show abstract

“…Sirtuin 6 contributes to YAP/TAZ deacetylation and reprograming the TEA domain transcription factor complex composition, thereby reducing the expression of downstream liver fibrosis targeting genes and ultimately delaying the development of liver fibrosis 264 . Furthermore, through using N‐acetyl‐l‐tryptophan in mice with CCl 4 ‐induced liver fibrosis, the TGF‐ β/Smad and Hippo/YAP signaling pathways were inhibited, and consequently, the expressions of α‐SMA and collagen I proteins were reduced, contributing to liver fibrosis improvement 265 . Indeed, fatty acids had also been found to participate in the activation of HSCs in liver fibrosis.…”

Section: Yap/taz and Fibrosismentioning

confidence: 99%

“… 264 Furthermore, through using N‐acetyl‐l‐tryptophan in mice with CCl 4 ‐induced liver fibrosis, the TGF‐ β/Smad and Hippo/YAP signaling pathways were inhibited, and consequently, the expressions of α‐SMA and collagen I proteins were reduced, contributing to liver fibrosis improvement. 265 Indeed, fatty acids had also been found to participate in the activation of HSCs in liver fibrosis. Exogenous fatty acids can enter the cells and become lipid droplets and activate MAPK13.…”

Section: Yap/taz and Fibrosismentioning

confidence: 99%

YAP/TAZ: Molecular pathway and disease therapy

Wei,

Hui,

Chen

et al. 2023

MedComm

View full text Add to dashboard Cite

The Yes‐associated protein and its transcriptional coactivator with PDZ‐binding motif (YAP/TAZ) are two homologous transcriptional coactivators that lie at the center of a key regulatory network of Hippo, Wnt, GPCR, estrogen, mechanical, and metabolism signaling. YAP/TAZ influences the expressions of downstream genes and proteins as well as enzyme activity in metabolic cycles, cell proliferation, inflammatory factor expression, and the transdifferentiation of fibroblasts into myofibroblasts. YAP/TAZ can also be regulated through epigenetic regulation and posttranslational modifications. Consequently, the regulatory function of these mechanisms implicates YAP/TAZ in the pathogenesis of metabolism‐related diseases, atherosclerosis, fibrosis, and the delicate equilibrium between cancer progression and organ regeneration. As such, there arises a pressing need for thorough investigation of YAP/TAZ in clinical settings. In this paper, we aim to elucidate the signaling pathways that regulate YAP/TAZ and explore the mechanisms of YAP/TAZ‐induce diseases and their potential therapeutic interventions. Furthermore, we summarize the current clinical studies investigating treatments targeting YAP/TAZ. We also address the limitations of existing research on YAP/TAZ and propose future directions for research. In conclusion, this review aims to provide fresh insights into the signaling mediated by YAP/TAZ and identify potential therapeutic targets to present innovative solutions to overcome the challenges associated with YAP/TAZ.

show abstract

Metabolomics and electronic tongue reveal the effects of different storage years on metabolites and taste quality of Oolong Tea

Sun

Zhang

et al. 2023

Food Control

View full text Add to dashboard Cite

N-Acetyl-l-tryptophan inhibits CCl4-induced hepatic fibrogenesis via regulating TGF-β1/SMAD and Hippo/YAP1 signal

Cited by 3 publications

References 48 publications

Single-cell RNA-seq reveals the role of YAP1 in prefrontal cortex microglia in depression

Single-cell RNA-seq reveals the role of YAP1 in prefrontal cortex microglia in depression

YAP/TAZ: Molecular pathway and disease therapy

Metabolomics and electronic tongue reveal the effects of different storage years on metabolites and taste quality of Oolong Tea

Contact Info

Product

Resources

About