title: An imbalance in Akt/mTOR is involved in the apoptotic and acantholytic processes in a mouse model of pemphigus vulgaris.
abstract: Pemphigus vulgaris (PV) is an autoimmune blistering disease characterized by the presence of IgG autoantibodies against Dsg3. Our aim was to investigate the molecular events implicated in the development and localization of apoptosis and acantholysis in PV. We used a passive transfer mouse model together with immunohistochemical (IHC) techniques and the TUNEL assay, with quantification analysis in the basal layer of the epidermis. The activated signalling molecules analysed and apoptotic cells detected showed an identical localization. Herein, we found for the first time in vivo an increased expression of activated HER receptor isoforms in the basal layer in PV lesions. Besides, we observed the almost total lack of activated Akt compared with a higher level of activated mTOR within the basal cells of the epidermis. Our observations strongly support that the restriction of acantholysis to the basal layer may be due, at least in part, to the selective and increased presence of activated HER receptor isoforms in these cells. After phosphorylation of HER receptor isoforms, intracellular signalling pathways are activated in the basal layer. In addition, the imbalance in Akt/mTOR that takes place in the basal cells may provide intracellular signals necessary for the development of apoptosis and acantholysis.
authors: Department of Dermatology, University Clinic of Navarra, School of Medicine, University of Navarra, Navarra, Spain.
authors: Maider
authors: M
authors: Pretel
authors: Agustín
authors: A
authors: España
authors: Miren
authors: M
authors: Marquina
authors: Beatriz
authors: B
authors: Pelacho
authors: Jose María
authors: JM
authors: López-Picazo
authors: Maria J
authors: MJ
authors: López-Zabalza
mesh_terms: D000051:Acantholysis; D000818:Animals; D017209:Apoptosis; D066259:Betacellulin; D002352:Carrier Proteins / Q000378:metabolism*; D004195:Disease Models, Animal; D004789:Enzyme Activation; D004815:Epidermal Growth Factor / Q000378:metabolism; D004817:Epidermis / Q000378:metabolism; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000069347:Erlotinib Hydrochloride; D006801:Humans; D007074:Immunoglobulin G; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D007428:Intradermal Tests; D007527:Isoenzymes / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010392:Pemphigus / Q000378:metabolism* / Q000503:physiopathology; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D011720:Pyrazoles; D011743:Pyrimidines; D011799:Quinazolines; D020123:Sirolimus; D058570:TOR Serine-Threonine Kinases; D016211:Transforming Growth Factor alpha / Q000378:metabolism; D019061:src-Family Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: C108123:4-amino-5-(4-methylphenyl)-7-(tert-butyl)pyrazolo(3,4-d)pyrimidine; C587851:BTC protein, human; D066259:Betacellulin; C587852:Btc protein, mouse; D002352:Carrier Proteins; D007074:Immunoglobulin G; D036341:Intercellular Signaling Peptides and Proteins; D007527:Isoenzymes; D011720:Pyrazoles; D011743:Pyrimidines; D011799:Quinazolines; D016211:Transforming Growth Factor alpha; D004815:Epidermal Growth Factor; D000069347:Erlotinib Hydrochloride; D017853:Phosphotransferases (Alcohol Group Acceptor); C546842:MTOR protein, human; C546843:mTOR protein, mouse; D066246:ErbB Receptors; D019061:src-Family Kinases; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus