YAP/TAZ as direct targets of Sirt6 deacetylase

Sirt6 ⏬YAP/TAZ-TEAD1 interaction ⏫VGLL4 (YAP/TAZ suppressor)-TEAD1 interaction

Both Lrat-Cre #HepaticStellateCell & Albumin-Cre Hepatocyte (or leaks to HSC?🤔) Sirt6 KO⏫Liver Fibrosis in MASH🐭

#FASEBJ 2022
faseb.onlinelibrary.wiley.com/doi/10.1096/...

#Senescence

E2F7 is methylated & stabilized (shunted away from ubiquitination) by Protein Arginine Methyltransferase 1

Sirt6 as a direct anti-senescent target gene in Smooth Muscle Cell

#FASEBJ 2025
faseb.onlinelibrary.wiley.com/doi/epdf/10....

Metabolome Atlas of Brain Reveals Regional Shared and Unique Metabolic Drifts in Response to Type 2 Diabetes in Male Mice A detailed metabolome atlas of the male mouse brain was established, incorporating metabolomic and lipidomic profiling of seven anatomical regions. T2D induced marked metabolic alterations, which wer...

Metabolome Atlas of Brain Reveals Regional Shared and Unique Metabolic Drifts in Response to Type 2 Diabetes in Male Mice #FASEBJ #MassSpec faseb.onlinelibrary.wiley.com/doi/10.1096/...

Spatial Metabolomics Reveals GLA‐Mediated Imbalance of Gal2Cer/GalCer as a Therapeutic Target in Myocardial Ischemia–Reperfusion Injury #FASEBJ #MassSpec faseb.onlinelibrary.wiley.com/doi/10.1096/...

#FGF9 or FGF2/4/8 ⏫UCP1 in both Brown & White Preadipocytes

FGF-induced UCP1 can be artificially activated by TTNPB
But NOT enhance browning or adipocytic differentiation per se

Non-conventional anti-inflamm effect of UCP1 in preadipocyte

#FASEBJ 2025
faseb.onlinelibrary.wiley.com/doi/10.1096/...

Altered Lipid Metabolism in the Vaginal Wall of Women With Pelvic Organ Prolapse: A Targeted Lipidomics Study This graphical abstract illustrates the association between pelvic organ prolapse (POP) and obesity. Vaginal anterior wall tissues were collected for targeted lipidomics analysis, revealing significa....

Altered Lipid Metabolism in the Vaginal Wall of Women With Pelvic Organ Prolapse: A Targeted Lipidomics Study #FASEBJ #MassSpec faseb.onlinelibrary.wiley.com/doi/10.1096/...

Spatial Metabolism of Primary Limited Cutaneous Amyloidosis Based on Mass Spectrometry Imaging In this study, metabolomic profiling was performed on skin tissues from patients with primary localized cutaneous amyloidosis (PLCA) and healthy controls (HC). The analysis identified several differe...

Spatial Metabolism of Primary Limited Cutaneous Amyloidosis Based on Mass Spectrometry Imaging #FASEBJ faseb.onlinelibrary.wiley.com/doi/10.1096/...

#YAP #Ferroptosis #SmoothMuscleCell #Atherosclerosis

Ferrostatin-1 in Apoe-/-🐭
⏬ferroptotic markers: Iron 4HNE COX2 GPX4
⏫lesion stability: necrotic core SMC Mφ collagen

SMC YAP1 ⬆️in unstable lesion or by oxLDL
YAP1-Glutaminase 1 in vitro

#FASEBJ 2024
faseb.onlinelibrary.wiley.com/doi/10.1096/...

O-GlcNAcylation OGT (O-GlcNAc transferase)⏫ #SmoothMuscleCell #Osteogenesis

SM22-CreERT::Ogt f/f🐭
⏬#MedialArterialCalcification (VitaminD3, 5/6 Nephrectomy)

O-GlcNAcylated β-catenin is protected from degradation & ⬆️SMC calcification😎

#FASEBJ 2024
faseb.onlinelibrary.wiley.com/doi/10.1096/...

Trophoblast to Spiral Artery Communication

Trophoblast-derived IL-1β⏫#EndothelialCell MMP10 secretion (likely help periendothelial matrix decomposition)

MMP10⏬ in decidua of🤰with high risk of #Preeclampsia

#FASEBJ 2025
faseb.onlinelibrary.wiley.com/doi/full/10....

How does Genomic Instability cause #VascularCalcification?

A potential STING-STAT1-NLRP3 #Inflammasome cascade in #SmoothMuscleCell Osteogenesis #MedialArterialCacification

Which type of DNA lesions activates STING in calcifying SMC?🧐

#FASEBJ 2025
faseb.onlinelibrary.wiley.com/doi/10.1096/...

#Piezo1 #YAP Bioenergetics

Human Umbilical Cord MSC

#CyclicStretch (10% strain, 0.5Hz, 7 d)
#Piezo➡️
YAP nuclear import➡️
⏫MFN1/2 ⏬DRP1➡️
⏫Mitochondrial fusion ⏫mtDNA-encoded genes➡️
⏫OXPHOS (⏫Glycolysis)➡️
⏫SMC contractile proteins

#FASEBJ 2025
faseb.onlinelibrary.wiley.com/doi/10.1096/...

Transcriptomic and lipidomic profiling reveals distinct bioactive lipid signatures in slow and fast muscles and highlights the role of resolvin‐D2 in fiber type determination during myogenesis Transcriptomics (bulk and single-nuclei RNAseq) and lipidomics (mass spectrometry) analysis showed that slow-twitch muscle (soleus) is enriched in bioactive lipids derived from docosahexaenoic acid (...

Congrats to #NicolasDumant & colleagues for their new #FASEBJ paper: Transcriptomic and lipidomic profiling reveals distinct bioactive lipid signatures in slow and fast muscles and highlights the role of resolvin-D2 in fiber type determination during myogenesis. #MyoBlue tinyurl.com/3ht6nr66

Multi‐omics analysis reveals alterations of breastmilk metabolites and proteins in Hong Kong lactating mothers Multi-omics analysis was applied in Hong Kong lactating mothers over the 12 months. The altered metabolic pathways included biotin/amino acid/fatty acid metabolism. The accumulation/remodeling of lip...

Multi-omics analysis reveals alterations of breastmilk metabolites and proteins in Hong Kong lactating mothers #FASEBJ #MassSpec faseb.onlinelibrary.wiley.com/doi/10.1096/...

#SmoothMuscleCell NRF2 KO🐭are susceptible to Angiotensin II-induced #AbdominalAorticAneurysm

NRF2-miR-145 cascade

scRNAseq👤AAA▶️7 SMC clusters
Contractile 1/2
Fibroblast-like
Macrophage-like
Stem cell-like
T cell-like
Plasma cell-like

#FASEBJ 2024
faseb.onlinelibrary.wiley.com/doi/10.1096/...

IL1β serves as a possible link b/w Trophoblast invasion & Uterine Spiral Artery #SmoothMuscleCell contractile phenotypic dynamics

Are the myometrial SMCs also affected similarly? 🥸

#FASEBJ 2024
faseb.onlinelibrary.wiley.com/doi/10.1096/...

Link b/w #LipidOxidation #Ferroptosis & #Calcification of #SmoothMuscleCell with #OxidizedPhospholipid POVPC

Ferrostatin-1 or mito-TEMPO⏬POVPC-induced SMC calcification

#FASEBJ 2024
faseb.onlinelibrary.wiley.com/doi/10.1096/...

Ohh😀
Sirtuin 6 protects against hepatic fibrogenesis by suppressing the YAP and TAZ function

LRAT+ #HepaticStellateCell Sirt6 KO-> increased TGFβ-SMAD3 + #YAP/TAZ activity

Similar or opposite in SMC?

#FASEBJ 2022
faseb.onlinelibrary.wiley.com/doi/full/10....

#MatrixStiffness & #PhosphatidicAcid enhance

#Senescence
#Mitochondria-ER contact
#ERStress
#MitochondriaDysfunction (JC-1)
#ROS
in #SmoothMuscleCell

Seem to be rescued by Atorvastatin (How?)🧐

#FASEBJ 2023
faseb.onlinelibrary.wiley.com/doi/10.1096/...