#TuberousSclerosisComplex #PulmonaryArterialHypertension

#MatrixStiffness 25 kPa-induced loss of TSC2 in PA #SmoothMuscleCell➡️
⏫mTOR & #YAP/TAZ➡️
⏫PASMC proliferation & ECM deposit (➡️fibroblast proliferation)

SM22a+ SMC het KO🐭of Tsc2➡️PAH at 9-wk

#SciSignal 2022
www.science.org/doi/10.1126/...

#YAP #Mechanoptosis #RigiditySensing

pTyr357 YAP, phospho by c-Abl/Src in #FocalAdhesion then translocated to Nuclei, ➡️Apoptosis of MDA-Tpm2.1; MEF on soft matrix 0.25kPa

Cellular sensing of #MatrixStiffness dictates proliferation/apoptosis switch of YAP

#CellRep 2024
www.cell.com/cell-reports...

Segregating AND Combining the impacts of Pressure (Ca2+) vs #MatrixStiffness (RhoA-LIMK) on #SmoothMuscleCell phenotypic plasticity

Converging on #Cofilin #Podosome Mechanosensing

Nice Intro to SMC #Mechanobiology🤓

#ScienceAdvances 2022
www.science.org/doi/10.1126/...

#MatrixStiffness controls hypertrophic responses of #SmoothMuscleCell to ANGII/Carbachol

12 kPa
ANGII⏬cell area, not cell volume/height (How🤔)
72 kPa
ANGII⏫cell area/volume, not height

#Piezo1-PKC-#Aquaporin1 cascade

#BrJPharmacol 2023
bpspubs.onlinelibrary.wiley.com/doi/10.1111/...

#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/...

#MatrixStiffness #Senescence

Passage-dependent senescent responses of cultured #CardiacFibroblast to Stiffness

Stiff hydrogel: 41 kPa
Soft: 6 kPa

Soft matrix⏫senescence (P2), ⏬TGFβ & ⏫NFκB-SASP (P5-6)

Timothy McKinsey lab #AJPHeartCirc 2023
journals.physiology.org/doi/abs/10.1...

Single-cell transcriptomics of #BoneMarrowMesenchymalStromalCell in response to #MatrixStiffness

2 vs 25 kPa
Adipo- vs osteogenic differentiation

TPM1/tropomyosin 1 as a Mechanotransducer upstream of #YAP
Dr. Oren Ram, Amnon Buxboim labs PNAS 2021
www.pnas.org/content/118/...

#MatrixStiffness drives #Pericyte-to-Myofibroblast transition in a microvessel culture model

A role of #EndothelialCell Mechanosensing (Integrinβ1) + TGFβ➡️

#Angiocrine (CTGF)➡️

Fibrotic phenotype of endothelia-associated Pericyte

#ATVB 2023
www.ahajournals.org/doi/10.1161/...