P2Y2 Receptor-Mediated Ca2+ Signaling and Spontaneous Ca2+ Releases in Human Valvular Myofibroblasts

Liang, Willmann; McDonald, Paul C.; McManus, Bruce M.; Breemen, Cornelis van; Wang, Xiaodong

doi:10.1536/ihj.49.221

Cited by 14 publications

(9 citation statements)

References 33 publications

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“…Another possible approach to assess the degree and type of intercellular coupling is to analyse Ca [i] oscillations with a frequency comparable with our observations (10-30 mHz), have been reported in fibroblastic cells only in response to various stimuli (Corps et al, 1989;Diliberto et al, 1994;Harootunian et al, 1991;Liang et al, 2003;Ridefelt et al, 1995;Uhlen et al, 2006;Wu et al, 2004). Our experiments establish for the first time that both cultured fibroblasts and myofibroblasts exhibit spontaneous and highly periodic Ca 2+ [i] oscillations, which occur with higher frequency in myofibroblasts.…”

Section: Discussionsupporting

confidence: 84%

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Myofibroblast communication is controlled by intercellular mechanical coupling

Follonier

Schaub

Meister

et al. 2008

Journal of Cell Science

109

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Neoformation of intercellular adherens junctions accompanies the differentiation of fibroblasts into contractile myofibroblasts, a key event during development of fibrosis and in wound healing. We have previously shown that intercellular mechanical coupling of stress fibres via adherens junctions improves contraction of collagen gels by myofibroblasts. By assessing spontaneous intracellular Ca2+ oscillations, we here test whether adherens junctions mechanically coordinate myofibroblast activities. Periodic Ca2+ oscillations are synchronised between physically contacting myofibroblasts and become desynchronised upon dissociation of adherens junctions with function-blocking peptides. Similar uncoupling is obtained by inhibiting myofibroblast contraction using myosin inhibitors and by blocking mechanosensitive ion channels using Gd3+ and GSMTx4. By contrast, gap junction uncouplers do not affect myofibroblast coordination. We propose the following model of mechanical coupling for myofibroblasts: individual cell contraction is transmitted via adherens junctions and leads to the opening of mechanosensitive ion channels in adjacent cells. The resulting Ca2+ influx induces a contraction that can feed back on the first cell and/or stimulate other contacting cells. This mechanism could improve the remodelling of cell-dense tissue by coordinating the activity of myofibroblasts.

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Section: Discussionsupporting

confidence: 84%

“…[i] oscillations have been described in different fibroblasts in response to various stimuli (Corps et al, 1989;Diliberto et al, 1994;Harootunian et al, 1991;Liang et al, 2003;Ridefelt et al, 1995;Uhlen et al, 2006;Wu et al, 2004) …”

Section: +mentioning

confidence: 99%

Myofibroblast communication is controlled by intercellular mechanical coupling

Follonier

Schaub

Meister

et al. 2008

Journal of Cell Science

109

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“…For certain experiments, valvular interstitial cells were used that had been isolated from noncalcified aortic valve leaflets (collected by the Cardiovascular Pathology Registry, St. Paul's Hospital, Vancouver, Canada) by enzymatic digestion, as we have previously described [28][29][30]. The valve leaflets were taken under ethics protocol from the explanted heart at the time of cardiac transplantation from a 47-yearold male patient with no history of heart valve disease.…”

Section: Cell Culturementioning

confidence: 99%

Versican localizes to the nucleus in proliferating mesenchymal cells

Carthy¹,

Abraham²,

Meredith³

et al. 2015

Cardiovascular Pathology

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“…In fibroblastic cells, single [Ca 2+ ] i increases lead to contractile responses within tens of seconds after chemical and mechanical stimulation (Follonier et al, 2008;Munevar et al, 2004 ] i oscillations with comparable frequencies have been reported to occur in different cultured fibroblasts after various stimuli (Arora et al, 1994;Chen et al, 2010;Diliberto et al, 1994;Harootunian et al, 1991;Liang et al, 2003;Ridefelt et al, 1995;Uhlen et al, 2006;Wu et al, 2004); however, cell contractile events were not assessed in these studies. Rhythmic cortical pulsations were described for fibroblasts in suspension (Salbreux et al, 2007) and for spreading fibroblasts after microtubule depolymerisation -in the latter case, preceded by [Ca 2+ ] i transients (Pletjushkina et al, 1756 Journal of Cell Science 123 (10) 2001).…”

mentioning

confidence: 90%

A new lock-step mechanism of matrix remodelling based on subcellular contractile events

Castella

Buscemi

Godbout

et al. 2010

Journal of Cell Science

112

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SummaryMyofibroblasts promote tissue contractures during fibrotic diseases. To understand how spontaneous changes in the intracellular calcium concentration, [Ca 2+ ] i , contribute to myofibroblast contraction, we analysed both [Ca 2+ ] i and subcellular contractions. Contractile events were assessed by tracking stress-fibre-linked microbeads and measured by atomic force microscopy. Myofibroblasts exhibit periodic (~100 seconds) [Ca 2+ ] i oscillations that control small (~400 nm) and weak (~100 pN) contractions. Whereas depletion of [Ca 2+ ] i reduces these microcontractions, cell isometric tension is unaffected, as shown by growing cells on deformable substrates. Inhibition of Rho-and ROCK-mediated Ca 2+ -independent contraction has no effect on microcontractions, but abolishes cell tension. On the basis of this two-level regulation of myofibroblast contraction, we propose a single-cell lock-step model. Rho-and ROCKdependent isometric tension generates slack in extracellular matrix fibrils, which are then accessible for the low-amplitude and highfrequency contractions mediated by [Ca 2+ ] i . The joint action of both contraction modes can result in macroscopic tissue contractures of ~1 cm per month.

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P2Y2 Receptor-Mediated Ca2+ Signaling and Spontaneous Ca2+ Releases in Human Valvular Myofibroblasts

Abstract: SUMMARY (Int Heart J 2008; 49: 221-236)

Cited by 14 publications

References 33 publications

Myofibroblast communication is controlled by intercellular mechanical coupling

Myofibroblast communication is controlled by intercellular mechanical coupling

Versican localizes to the nucleus in proliferating mesenchymal cells

A new lock-step mechanism of matrix remodelling based on subcellular contractile events

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