Cell-cell contact and matrix adhesion promote αSMA expression during TGFβ1-induced epithelial-myofibroblast transition via Notch and MRTF-A

O’Connor, Joseph W.; Mistry, Krunal; Detweiler, Dayne; Wang, Clayton; Gomez, Esther W.

doi:10.1038/srep26226

Cited by 32 publications

(27 citation statements)

References 45 publications

(82 reference statements)

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“…A common feature of MRTF-A and YAP regulation is the pronounced influence of cell density on the subcellular distribution pattern of these transcription factors. This has previously been reported for various cell lines (Zhao et al, 2007;Mateus et al, 2015;O'Connor et al, 2016), and could be reproduced with primary endothelial cells under standard cell culture conditions in our laboratory ( Fig. S2).…”

Section: The Adhesive Surface Area and Projected Nuclear Area Positivsupporting

confidence: 83%

Micropatterning as a tool to identify regulatory triggers and kinetics of actin-mediated endothelial mechanosensing

Gegenfurtner

Jahn

Wagner³

et al. 2018

Journal of Cell Science

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Developmental processes, such as angiogenesis, are associated with a constant remodeling of the actin cytoskeleton in response to different mechanical stimuli. The mechanosensitive transcription factors MRTF-A (MKL1) and YAP (also known as YAP1) are important mediators of this challenging adaptation process. However, it is as yet unknown whether both pathways respond in an identical or in a divergent manner to a given microenvironmental guidance cue. Here, we use a micropatterning approach to dissect single aspects of cellular behavior in a spatiotemporally controllable setting. Using the exemplary process of angiogenesis, we show that cell-cell contacts and adhesive surface area are shared regulatory parameters of MRTF and YAP on rigid 2D surfaces. By analyzing MRTF and YAP under laminar flow conditions and during cell migration on dumbbell-shaped microstructures, we demonstrate that they exhibit different translocation kinetics. In conclusion, our work promotes the application of micropatterning techniques as a cell biological tool to study mechanosensitive signaling in the context of angiogenesis.

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Section: The Adhesive Surface Area and Projected Nuclear Area Positivsupporting

confidence: 83%

Micropatterning as a tool to identify regulatory triggers and kinetics of actin-mediated endothelial mechanosensing

Gegenfurtner

Jahn

Wagner³

et al. 2018

Journal of Cell Science

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“…In the condition of normal gravity, loss of cell-cell adhesion was accompanied by the increase of cell-ECM interaction when cells undergoing epithelial-mesenchymal transition [36]. However, after treatment of cells in SMG for three days, both the impaired cell-cell adhesion characterized by the down-regulation of E-cadherin and cell-ECM adhesion characterized by reduced expression of integrin-β1 were observed.…”

Section: Discussionmentioning

confidence: 96%

EMT Transcription Factors Are Involved in the Altered Cell Adhesion under Simulated Microgravity Effect or Overloading by Regulation of E-cadherin

Shi

Cao

et al. 2020

IJMS

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In order to study the effect of stress changes on cell adhesion, HUVEC, and MCF-7 cells were treated with simulated microgravity effect (SMG) and overloading (OL). Methods: Rotating Wall Vessel (2D-RWVS) bioreactor was used to create different culture conditions. In addition, the alteration of cell adhesion states, adhesion proteins, and relating factors of adhesion molecules under these two conditions were detected using cell adhesion assay, immunofluorescence, western blot, and qRT-PCR technology. Results: The results showed that the adhesion of cells decreased under SMG, while increased under OL. The expressions of integrin β1, paxillin, and E-cadherin under SMG condition were down-regulated as compared to that of the control group showing a time-dependent pattern of the decreasing. However, under OL condition, the expressions of adhesion proteins were up-regulated as compared to that of the control group, with a time-dependent pattern of increasing. EMT transcription factors Snail, twist, and ZEB1 were up-regulated under SMG while down-regulated under OL. Conclusion: Collectively our results indicated that cells could respond to stress changes to regulate the expressions of adhesion proteins and adapt their adhesion state to the altered mechanical environment. The altered cell adhesion in response to the mechanical stress may involve the changed expression of EMT-inducing factors, Snail, Twist, and ZEB1under the SMG/OL conditions.

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“…[19] During physiological wound healing process, myofibroblasts undergo apoptosis. [20,21,22,23]. On the contrary, the addition of exogenous TGF-β1 on passage 3 resulted in significantly low α-SMA.…”

Section: Resultsmentioning

confidence: 86%

α-SMA Expression Increased Over Cell Passages and Decreased by Exogenous TGF-β1, In Vitro Studies on Myofibroblast Derived from Orbital Socket Contracture

Dewi

Chairinnisa²,

Sujuti³

et al. 2018

J.Trop.Life.Science

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ABSTRACTα-smooth muscle actin (α-SMA), a marker of myofibroblast, induces cytoskeleton reorganization, increases contractility and stimulates cell migration in TGF-β1 induced stress fibers. The aims of the present study were to determine the level of α-SMA expression and morphological cell changes in different passages of myofibroblasts with varied TGF-β1 concentrations. Myofibroblast cell cultures were derived from fibrotic tissues of fourth degree socket contracture. The α-SMA expression level was measured in myofibroblast cultures passage I, II, and III with and without 10 ng/mL TGF-β1, and in passage III with 2.5; 5; 10; and 20 ng/mL TGF-β1. Results: The levels of α-SMA expression level in passage I to III were I 31.42 ± 3.4; 40.34 ± 8.14 and 56.37 ± 7.57, respectively. Addition of 10 ng/mL TGF-β1 into passage I-III myofibroblast cultures resulted in α-SMA expression level of 31.24 ± 2.93; 36.81 ± 6.09; and 14.29 ± 2.72, respectively. Myoblasts passage III showed the lowest α-SMA expression level following exposure to TGF-β1 10 ng/mL (22.37 ± 12.86) and highest without TGF-β1 (48.34 ± 13.36), however no morphological changes detected. α-SMA expression level increased with cell passages, decreases with addition of TGF-β1 while not affecting morphology of myofibroblast derived from the orbital socket contracture.

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Cell-cell contact and matrix adhesion promote αSMA expression during TGFβ1-induced epithelial-myofibroblast transition via Notch and MRTF-A

Cited by 32 publications

References 45 publications

Micropatterning as a tool to identify regulatory triggers and kinetics of actin-mediated endothelial mechanosensing

Micropatterning as a tool to identify regulatory triggers and kinetics of actin-mediated endothelial mechanosensing

EMT Transcription Factors Are Involved in the Altered Cell Adhesion under Simulated Microgravity Effect or Overloading by Regulation of E-cadherin

α-SMA Expression Increased Over Cell Passages and Decreased by Exogenous TGF-β1, In Vitro Studies on Myofibroblast Derived from Orbital Socket Contracture

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