#Sirt6 deacetylates #YAP & #TAZ->
⏬their transcriptional activities
⏬TGFβ1-induced Fibrotic reprogramming of #HepaticStellateCell
in diet-induced🐭#LiverFibrosis

TAZ seems more sensitive to Sirt6 than YAP🤓

#MALFD

Dr. Charlie Dong lab FASEB J 2022
https://faseb.onlinelibrary.wiley.com/doi/full/10.1096/fj.202200522R

#EndothelialCell #Sirt6 deficiency->
⏫#TissueFactor/F3+vascular inflammation genes Cox2, VCAM1, TNFα, MCP1
Accelerated Carotid arterial #Thrombosis (Rose bengal)

A role in atherosclerotic plaque stability?😃

Dr. Christian Matter lab JMCC 2022
https://www.jmcc-online.com/article/S0022-2828(22)00565-X/fulltext

#Sirt6 #Osteoarthritis

Sirt6⏬#Senescence & IL15-JAK3-STAT5-inflammation in adult #Chondrocyte

Deacetylated STAT5 by Sirt6 fails nuclear import

In contrast, Sirt6⏫p21->Senescence in embryonic chondrocyte

Dr. Ming-liang Ji & Jun Lu lab Nature Comms 2022
https://www.nature.com/articles/s41467-022-35424-w

An interesting chondrotrophic nanoparticle is used to deliver MDL-800, Sirt6 activator, in🐭DMM #Osteoarthritis

Chondrocyte-specific aptamer tgg2-functionalized PEGylated PAMAM nanoparticle

Originally used for microRNA Annals of the Rheumatic Diseases 2021
https://ard.bmj.com/content/80/3/356.abstract

#Sirt6 control of #EndothelialCell #FattyAcid transport links #Diabetes microvascular dysfunction with #HeartFailurewithPreservedEjectionFraction #HFpEF

EC Sirt6->
⏬H3K9ac PPARγ promoter
⏬CD36,FABP4/5
⏬🐭 Heart Lipid

Dr. Zheng Gen Jin lab Circ Res 2022
https://www.ahajournals.org/doi/10.1161/CIRCRESAHA.121.318988

#Sirt6 #VascularInflammation

MRTF-A as a deacetylation target of Sirt6 in #EndothelialCell

Deactylated MRTF-A stays in cytoplasm, failing to mediate oxLDL-induced EC ICAM1

An OxLDL-DNMT1 cacade epigenetically silences Sirt6 expression

Dr. Qianyun Wang, Tianfa Li & Qianwen Zhao labs Cell Death Discov 2022
https://www.nature.com/articles/s41420-022-00903-y

#SIRT6 N308K/A313S, a #Centenarian variant
⏬deacetylase/deacylase
⏫mono-ADP-ribosylase
⏬LINE1 retrotransposition
⏫DNA repair
⏫tumor killing

Lamin A is mADP-ribosylated by Sirt6!

Love to explore its benefit over blood vessels!

Dr. Andrei Seluanov, Yousin Suh, Vera Gorbunova labs EMBO J 2022
https://www.embopress.org/doi/full/10.15252/embj.2021110393

12q, an optimized small chemical activator of #Sirt6
Comprehensive analyses vs MDL-800->
⏫Sirt6 deacetylase & demyristoylase activities
⏫Anti-#PancreaticDuctalAdenoCarcinoma activity

Look forward to more studies on its Non-tumoral benefits?🧐

Dr. Shengyong Yang lab J Med Chem 2022
https://pubs.acs.org/doi/full/10.1021/acs.jmedchem.0c01183