Regulation of tgfβ signalling by trpv4 in chondrocytes

Steven Woods; Paul A. Humphreys; Nicola Bates; Sophie Alice Richardson; Shweta Yogesh Kuba; Imogen R. Brooks; Stuart A. Cain; Susan J. Kimber

doi:10.3390/cells10040726

Regulation of tgfβ signalling by trpv4 in chondrocytes

Steven Woods, Paul A. Humphreys, Nicola Bates, Sophie Alice Richardson, Shweta Yogesh Kuba, Imogen R. Brooks, Stuart A. Cain, Susan J. Kimber

SHLS Life Sciences

Research output: Contribution to journal › Article › peer-review

3 Citations (Scopus)

Abstract

The growth factor TGFβ and the mechanosensitive calcium‐permeable cation channel TRPV4 are both important for the development and maintenance of many tissues. Although TRPV4 and TGFβ both affect core cellular functions, how their signals are integrated is unknown. Here we show that pharmacological activation of TRPV4 significantly increased the canonical response to TGFβ stimulation in chondrocytes. Critically, this increase was only observed when TRPV4 was activated after, but not before TGFβ stimulation. The increase was prevented by pharmacological TRPV4 inhibition or knockdown and is calcium/CamKII dependent. RNA‐seq analysis after TRPV4 activation showed enrichment for the TGFβ signalling pathway and identified JUN and SP1 as key transcription factors involved in this response. TRPV4 modulation of TGFβ signalling represents an important pathway linking mechanical signalling to tissue development and homeostasis.

Original language	English
Article number	726
Number of pages	19
Journal	Cells
Volume	10
Issue number	4
DOIs	https://doi.org/10.3390/cells10040726
Publication status	Published - 24 Mar 2021

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© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

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title = "Regulation of tgfβ signalling by trpv4 in chondrocytes",

abstract = "The growth factor TGFβ and the mechanosensitive calcium‐permeable cation channel TRPV4 are both important for the development and maintenance of many tissues. Although TRPV4 and TGFβ both affect core cellular functions, how their signals are integrated is unknown. Here we show that pharmacological activation of TRPV4 significantly increased the canonical response to TGFβ stimulation in chondrocytes. Critically, this increase was only observed when TRPV4 was activated after, but not before TGFβ stimulation. The increase was prevented by pharmacological TRPV4 inhibition or knockdown and is calcium/CamKII dependent. RNA‐seq analysis after TRPV4 activation showed enrichment for the TGFβ signalling pathway and identified JUN and SP1 as key transcription factors involved in this response. TRPV4 modulation of TGFβ signalling represents an important pathway linking mechanical signalling to tissue development and homeostasis.",

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T1 - Regulation of tgfβ signalling by trpv4 in chondrocytes

AU - Woods, Steven

AU - Humphreys, Paul A.

AU - Bates, Nicola

AU - Richardson, Sophie Alice

AU - Kuba, Shweta Yogesh

AU - Brooks, Imogen R.

AU - Cain, Stuart A.

AU - Kimber, Susan J.

PY - 2021/3/24

Y1 - 2021/3/24

N2 - The growth factor TGFβ and the mechanosensitive calcium‐permeable cation channel TRPV4 are both important for the development and maintenance of many tissues. Although TRPV4 and TGFβ both affect core cellular functions, how their signals are integrated is unknown. Here we show that pharmacological activation of TRPV4 significantly increased the canonical response to TGFβ stimulation in chondrocytes. Critically, this increase was only observed when TRPV4 was activated after, but not before TGFβ stimulation. The increase was prevented by pharmacological TRPV4 inhibition or knockdown and is calcium/CamKII dependent. RNA‐seq analysis after TRPV4 activation showed enrichment for the TGFβ signalling pathway and identified JUN and SP1 as key transcription factors involved in this response. TRPV4 modulation of TGFβ signalling represents an important pathway linking mechanical signalling to tissue development and homeostasis.

AB - The growth factor TGFβ and the mechanosensitive calcium‐permeable cation channel TRPV4 are both important for the development and maintenance of many tissues. Although TRPV4 and TGFβ both affect core cellular functions, how their signals are integrated is unknown. Here we show that pharmacological activation of TRPV4 significantly increased the canonical response to TGFβ stimulation in chondrocytes. Critically, this increase was only observed when TRPV4 was activated after, but not before TGFβ stimulation. The increase was prevented by pharmacological TRPV4 inhibition or knockdown and is calcium/CamKII dependent. RNA‐seq analysis after TRPV4 activation showed enrichment for the TGFβ signalling pathway and identified JUN and SP1 as key transcription factors involved in this response. TRPV4 modulation of TGFβ signalling represents an important pathway linking mechanical signalling to tissue development and homeostasis.

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U2 - 10.3390/cells10040726

DO - 10.3390/cells10040726

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JO - Cells

JF - Cells

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Regulation of tgfβ signalling by trpv4 in chondrocytes

Abstract

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