Dimensionality changes actin network through lamin A and C and zyxin

Zonderland, Jip; Moldero, Ivan Lorenzo; Mota, Carlos; Moroni, Lorenzo

doi:10.1101/752691

Cited by 6 publications

(10 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[14][15][16][17] We have previously shown that hMSCs in 3D electrospun (ESP) scaffolds have fewer stress fibers and focal adhesions than in 2D. 35,36 We have also seen that 3D alginate hydrogels show the same trend, in line with results published by others. [37][38][39][40][41][42][43][44][45] Indeed, when stained for zyxin, hMSCs cultured in 3D RGD-modified alginate hydrogels or 3D ESP scaffolds displayed very few zyxin positive focal adhesions, while many large focal adhesions were observed in 2D TCP ( Figure 4A).…”

Section: Increased Stc1 Secretion In 3d Culturessupporting

confidence: 88%

“…A reduced number of focal adhesions and actin stress fibers have been previously reported in a number of studies in both hydrogels [37][38][39][40][41][42][43][44][45] and ESP scaffolds. 35,36 The increase of STC1 in 3D cultures has been shown before in different 3D culture systems. [14][15][16][17] Our data suggest that this might be due to a reduction in focal adhesions and/or actin-myosin tension.…”

Section: Discussionsupporting

confidence: 57%

See 1 more Smart Citation

Mechanosensitive regulation of stanniocalcin-1 by zyxin and actin-myosin in human mesenchymal stromal cells

et al. 2020

Self Cite

View full text Add to dashboard Cite

Stanniocalcin-1 (STC1) secreted by mesenchymal stromal cells (MSCs) has antiinflammatory functions, reduces apoptosis, and aids in angiogenesis, both in vitro and in vivo. However, little is known about the molecular mechanisms of its regulation. Here, we show that STC1 secretion is increased only under specific cell-stress conditions. We find that this is due to a change in actin stress fibers and actin-myosin tension. Abolishment of stress fibers by blebbistatin and knockdown of the focal adhesion protein zyxin leads to an increase in STC1 secretion. To also study this connection in 3D, where few focal adhesions and actin stress fibers are present, STC1 expression was analyzed in 3D alginate hydrogels and 3D electrospun scaffolds. Indeed, STC1 secretion was increased in these low cellular tension 3D environments. Together, our data show that STC1 does not directly respond to cell stress, but that it is regulated through mechanotransduction. This research takes a step forward in the fundamental understanding of STC1 regulation and can have implications for cell-based regenerative medicine, where cell survival, anti-inflammatory factors, and angiogenesis are critical.

show abstract

Section: Increased Stc1 Secretion In 3d Culturessupporting

confidence: 88%

Section: Discussionsupporting

confidence: 57%

Mechanosensitive regulation of stanniocalcin-1 by zyxin and actin-myosin in human mesenchymal stromal cells

et al. 2020

Self Cite

View full text Add to dashboard Cite

show abstract

“…Indeed, the optimal stiffness for differentiation and proliferation defer per cell type [56,57] . We have previously shown that hMSCs experience the ESP scaffolds used here as a soft substrate, demonstrated by fewer focal adhesions, less lamin A/C and less YAP nuclear translocation [58] . The difference in focal adhesion formation between hMSCs and fibroblasts observed here potentially derives from a different response to matrix stiffness.…”

Section: Discussionmentioning

confidence: 90%

Mechanosensitive regulation of FGFR1 through the MRTF-SRF pathway

Zonderland

Rezzola

Moroni

2019

Preprint

Self Cite

View full text Add to dashboard Cite

Controlling basic fibroblast growth factor (bFGF) signaling is important for both tissueengineering purposes, controlling proliferation and differentiation potential, and for cancer biology, influencing tumor progression and metastasis. Here, we observed that human mesenchymal stromal cells (hMSCs) no longer responded to soluble or covalently bound bFGF when cultured on microfibrillar substrates, while fibroblasts did. This correlated with a downregulation of FGF receptor 1 (FGFR1) expression of hMSCs on microfibrillar substrates, compared to hMSCs on conventional tissue culture plastic (TCP). hMSCs also expressed less SRF on ESP scaffolds, compared to TCP, while fibroblasts maintained high FGFR1 and SRF expression. Inhibition of actin-myosin tension or the MRTF/SRF pathway decreased FGFR1 expression in hMSCs, fibroblasts and MG63 osteosarcoma cells. This downregulation was functional, as hMSCs became irresponsive to bFGF in the presence of MRTF/SRF inhibitor. Together, our data show that hMSCs, but not fibroblasts, are irresponsive to bFGF when cultured on microfibrillar susbtrates by downregulation of FGFR1 through the MRTF/SRF pathway. This is the first time FGFR1 expression has been shown to be mechanosensitive and adds to the sparse literature on FGFR1 regulation. These results could open up new targets for cancer treatments and could aid designing tissue engineering constructs that better control cell proliferation.

show abstract

“…While actin-myosin inhibition by blebbistatin did decrease FGFR1 expression, zyxin knockdown did not. Although fewer than normally, zyxin knockdown cells still form focal adhesions 25,40 . Our data suggests that the actin-myosin tension between these focal adhesions is still sufficient to maintain a higher FGFR1 expression, as full inhibition of actin-myosin by blebbistatin reduced FGFR1.…”

Section: Discussionmentioning

confidence: 94%

“…As transplanted cells for regenerative medicine inevitably end up in a 3D environment, we wanted to investigate the potential mechanosensitive regulation of FGFR1 and response to bFGF in 3D. Previously, we have shown that hMSCs reduce cellular tension in 3D microfibrillar substrates and other 3D environments 25 . Thus, to investigate the effect of bFGF in 3D and to potentially find leads on FGFR1 regulation, we started by investigating the response of hMSCs to bFGF in a 3D microfibrillar environment.…”

mentioning

confidence: 99%

Actomyosin and the MRTF-SRF pathway downregulate FGFR1 in mesenchymal stromal cells

2020

Self Cite

View full text Add to dashboard Cite

Both biological and mechanical signals are known to influence cell proliferation. However, biological signals are mostly studied in two-dimensions (2D) and the interplay between these different pathways is largely unstudied. Here, we investigated the influence of the cell culture environment on the response to bFGF, a widely studied and important proliferation growth factor. We observed that human mesenchymal stromal cells (hMSCs), but not fibroblasts, lose the ability to respond to soluble or covalently bound bFGF when cultured on microfibrillar substrates. This behavior correlated with a downregulation of FGF receptor 1 (FGFR1) expression of hMSCs on microfibrillar substrates. Inhibition of actomyosin or the MRTF/SRF pathway decreased FGFR1 expression in hMSCs, fibroblasts and MG63 cells. To our knowledge, this is the first time FGFR1 expression is shown to be regulated through a mechanosensitive pathway in hMSCs. These results add to the sparse literature on FGFR1 regulation and potentially aid designing tissue engineering constructs that better control cell proliferation.

show abstract

Dimensionality changes actin network through lamin A and C and zyxin

Cited by 6 publications

References 42 publications

Mechanosensitive regulation of stanniocalcin-1 by zyxin and actin-myosin in human mesenchymal stromal cells

Mechanosensitive regulation of stanniocalcin-1 by zyxin and actin-myosin in human mesenchymal stromal cells

Mechanosensitive regulation of FGFR1 through the MRTF-SRF pathway

Actomyosin and the MRTF-SRF pathway downregulate FGFR1 in mesenchymal stromal cells

Contact Info

Product

Resources

About