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- Title
Regulation of TGFβ Signalling by TRPV4 in Chondrocytes.
- Authors
Woods, Steven; Humphreys, Paul A.; Bates, Nicola; Richardson, Sophie Alice; Kuba, Shweta Yogesh; Brooks, Imogen R.; Cain, Stuart A.; Kimber, Susan J.; Inman, Gareth; Kalyuzhny, Alexander E.
- 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.
- Subjects
CARTILAGE cells; TRANSCRIPTION factor Sp1; TRP channels; HOMEOSTASIS
- Publication
Cells (2073-4409), 2021, Vol 10, Issue 4, p726
- ISSN
2073-4409
- Publication type
Article
- DOI
10.3390/cells10040726