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PMID:18398001

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Citation

Feutz, AC, Barrandon, Y and Monard, D (2008) Control of thrombin signaling through PI3K is a mechanism underlying plasticity between hair follicle dermal sheath and papilla cells. J. Cell. Sci. 121:1435-43

Abstract

In hair follicles, dermal papilla (DP) and dermal sheath (DS) cells exhibit striking levels of plasticity, as each can regenerate both cell types. Here, we show that thrombin induces a phosphoinositide 3-kinase (PI3K)-Akt pathway-dependent acquisition of DS-like properties by DP cells in vitro, involving increased proliferation rate, acquisition of ;myofibroblastic' contractile properties and a decreased capacity to sustain growth and survival of keratinocytes. The thrombin inhibitor protease nexin 1 [PN-1, also known as SERPINE2) regulates all those effects in vitro. Accordingly, the PI3K-Akt pathway is constitutively activated and expression of myofibroblastic marker smooth-muscle actin is enhanced in vivo in hair follicle dermal cells from PN-1(-/-) mice. Furthermore, physiological PN-1 disappearance and upregulation of the thrombin receptor PAR-1 (also known as F2R) during follicular regression in wild-type mice also correlate with such changes in DP cell characteristics. Our results indicate that control of thrombin signaling interferes with hair follicle dermal cells plasticity to regulate their function.

Links

PubMed Online version:10.1242/jcs.018689

Keywords

Amyloid beta-Protein Precursor/metabolism; Animals; Cell Proliferation; Cells, Cultured; Dermis/cytology; Dermis/enzymology; Enzyme Activation; Fibroblasts/cytology; Fibroblasts/enzymology; Hair Follicle/cytology; Hair Follicle/enzymology; Hair Follicle/growth & development; Mice; Phenotype; Phosphatidylinositol 3-Kinases/metabolism; Protease Nexins; Protein Transport; Proto-Oncogene Proteins c-akt/metabolism; Receptors, Cell Surface/metabolism; Signal Transduction; Thrombin/antagonists & inhibitors; Thrombin/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:THRB

acts_upstream_of_or_within

GO:0030307: positive regulation of cell growth

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:101780

P

Seeded From UniProt

complete

MOUSE:THRB

acts_upstream_of_or_within

GO:0008284: positive regulation of cell population proliferation

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:101780

P

Seeded From UniProt

complete

MOUSE:THRB

acts_upstream_of_or_within

GO:0014068: positive regulation of phosphatidylinositol 3-kinase signaling

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:101780
MGI:MGI:101802

P

Seeded From UniProt

complete

MOUSE:THRB

acts_upstream_of_or_within

GO:0008360: regulation of cell shape

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:101780

P

Seeded From UniProt

complete

MOUSE:THRB

enables

GO:0004252: serine-type endopeptidase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:THRB

enables

GO:0004252: serine-type endopeptidase activity

ECO:0000314: direct assay evidence used in manual assertion

F

  • occurs_in:(EMAPA:26720)
  • has_input:(MGI:MGI:88380)

Seeded From UniProt

complete

MOUSE:THRB

acts_upstream_of_or_within

GO:0070493: thrombin-activated receptor signaling pathway

ECO:0000266: sequence orthology evidence used in manual assertion

MGI:MGI:101802

P

Seeded From UniProt

complete

MOUSE:GDN

acts_upstream_of_or_within

GO:0030308: negative regulation of cell growth

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:88380

P

Seeded From UniProt

complete

MOUSE:GDN

acts_upstream_of_or_within

GO:0008285: negative regulation of cell population proliferation

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:88380

P

Seeded From UniProt

complete

MOUSE:GDN

acts_upstream_of_or_within

GO:0014067: negative regulation of phosphatidylinositol 3-kinase signaling

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:88380

P

Seeded From UniProt

complete

MOUSE:GDN

acts_upstream_of_or_within

GO:0010466: negative regulation of peptidase activity

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2387774

P

  • regulates_o_occurs_in:(EMAPA:26720)
  • has_input:(MGI:MGI:88380)

Seeded From UniProt

complete

MOUSE:PAR1

acts_upstream_of_or_within

GO:0070493: thrombin-activated receptor signaling pathway

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:88380

P

Seeded From UniProt

complete

MOUSE:PAR1

acts_upstream_of_or_within

GO:0014068: positive regulation of phosphatidylinositol 3-kinase signaling

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:88380

P

Seeded From UniProt

complete


See also

References

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