RESUMEN
Acrokeratosis paraneoplastica (Basex syndrome) is a rare paraneoplastic condition hallmarked by psoriasiform lesion development on acral surfaces, most often related to an underlying squamous cell carcinoma. Patients may also present with nail plate changes. Successful management of this condition can be accomplished by treating the underlying malignancy.
Asunto(s)
Carcinoma de Células Escamosas , Neoplasias Pulmonares , Enfermedades de la Uña , Síndromes Paraneoplásicos , Neoplasias Cutáneas , Humanos , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/complicaciones , Carcinoma de Células Escamosas/patología , Síndromes Paraneoplásicos/diagnóstico , Síndromes Paraneoplásicos/patología , Neoplasias Pulmonares/complicaciones , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patología , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/complicaciones , Enfermedades de la Uña/patología , Enfermedades de la Uña/diagnóstico , Enfermedades de la Uña/etiología , Masculino , Anciano , Persona de Mediana Edad , Carcinoma Basocelular , HipotricosisAsunto(s)
Hidroxicloroquina , Nivolumab , Enfermedades del Pene , Anciano , Humanos , Masculino , Antineoplásicos Inmunológicos/efectos adversos , Erupciones por Medicamentos/etiología , Erupciones por Medicamentos/patología , Hidroxicloroquina/efectos adversos , Erupciones Liquenoides/inducido químicamente , Erupciones Liquenoides/patología , Nivolumab/efectos adversos , Enfermedades del Pene/inducido químicamente , Enfermedades del Pene/tratamiento farmacológico , Enfermedades del Pene/patología , Úlcera Cutánea/inducido químicamente , Úlcera Cutánea/patologíaRESUMEN
Type II alveolar epithelial cell (AECII) redox imbalance contributes to the pathogenesis of idiopathic pulmonary fibrosis (IPF), a deadly disease with limited treatment options. Here, we show that expression of membrane-bound cytochrome B5 reductase 3 (CYB5R3), an enzyme critical for maintaining cellular redox homeostasis and soluble guanylate cyclase (sGC) heme iron redox state, is diminished in IPF AECIIs. Deficiency of CYB5R3 in AECIIs led to sustained activation of the pro-fibrotic factor TGF-ß1 and increased susceptibility to lung fibrosis. We further show that CYB5R3 is a critical regulator of ERK1/2 phosphorylation and the sGC/cGMP/protein kinase G axis that modulates activation of the TGF-ß1 signaling pathway. We demonstrate that sGC agonists (BAY 41-8543 and BAY 54-6544) are effective in reducing the pulmonary fibrotic outcomes of in vivo deficiency of CYB5R3 in AECIIs. Taken together, these results show that CYB5R3 in AECIIs is required to maintain resilience after lung injury and fibrosis and that therapeutic manipulation of the sGC redox state could provide a basis for treating fibrotic conditions in the lung and beyond.