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Inhibition of Rho A activity causes pemphigus skin blistering.
- Source :
-
The Journal of cell biology [J Cell Biol] 2006 Dec 04; Vol. 175 (5), pp. 721-7. Date of Electronic Publication: 2006 Nov 27. - Publication Year :
- 2006
-
Abstract
- The autoimmune blistering skin diseases pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are mainly caused by autoantibodies against desmosomal cadherins. In this study, we provide evidence that PV-immunoglobulin G (IgG) and PF-IgG induce skin blistering by interference with Rho A signaling. In vitro, pemphigus IgG caused typical hallmarks of pemphigus pathogenesis such as epidermal blistering in human skin, cell dissociation, and loss of desmoglein 1 (Dsg 1)-mediated binding probed by laser tweezers. These changes were accompanied by interference with Rho A activation and reduction of Rho A activity. Pemphigus IgG-triggered keratinocyte dissociation and Rho A inactivation were p38 mitogen-activated protein kinase dependent. Specific activation of Rho A by cytotoxic necrotizing factor-y abolished all pemphigus-triggered effects, including keratin retraction and release of Dsg 3 from the cytoskeleton. These data demonstrate that Rho A is involved in the regulation of desmosomal adhesion, at least in part by maintaining the cytoskeletal anchorage of desmosomal proteins. This may open the possibility of pemphigus treatment with the epidermal application of Rho A agonists.
- Subjects :
- Blister enzymology
Cadherins metabolism
Cell Line
Desmoglein 1 metabolism
Desmoglein 3 metabolism
Desmosomes enzymology
Desmosomes physiology
Enzyme Activation
Humans
Keratin-14 metabolism
Keratinocytes pathology
Pemphigus enzymology
Pemphigus immunology
Signal Transduction
Skin metabolism
Blister etiology
Immunoglobulin G physiology
Pemphigus etiology
Skin pathology
rhoA GTP-Binding Protein metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0021-9525
- Volume :
- 175
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- The Journal of cell biology
- Publication Type :
- Academic Journal
- Accession number :
- 17130286
- Full Text :
- https://doi.org/10.1083/jcb.200605125