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Editorial
. 2017 Aug 8;136(6):562-565.
doi: 10.1161/CIRCULATIONAHA.117.028957.

p38α: A Profibrotic Signaling Nexus

Matthew S Stratton  1 , Keith A Koch  1 , Timothy A McKinsey  2
Affiliations
Editorial

p38α: A Profibrotic Signaling Nexus

Matthew S Stratton et al. Circulation. .
No abstract available

Keywords: Editorials; fibrosis; heart; inhibitor; kinase; myofibroblast.

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Conflict of interest statement

Conflict of Interest Disclosures

None

Figures

Figure
Figure. A model for the regulation of myofibroblast differentiation and fibrosis by p38α
Within fibroblasts, p38α promotes serum response factor (SRF) transcriptional activity and enhances calcineurin-nuclear factor of activated T cells (NFAT) signaling via canonical transient receptor potential 6 (TRPC6). Together, SRF and NFAT activate genes that promote myofibroblast differentiation and fibrosis. SRF and NFAT also stimulate TRPC6 expression, creating a pro-fibrotic positive feedback loop, and appear to promote expression of factors that function in a paracrine manner to stimulate cardiac hypertrophy. Small molecule inhibitors of p38α or upstream kinases such as apoptosis signal-regulating kinase 1 (ASK1) have the potential to block cardiac fibrosis.
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References

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