Assuntos
DNA/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Ceratodermia Palmar e Plantar/genética , Mutação , Adulto , Biópsia , Análise Mutacional de DNA , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Ceratodermia Palmar e Plantar/diagnóstico , Ceratodermia Palmar e Plantar/metabolismo , Linhagem , Couro Cabeludo , Pele/metabolismo , Pele/patologiaRESUMO
Chronic rhinosinusitis with nasal polyps is considered a subgroup of chronic rhinosinusitis and a significant health problem, but the pathogenesis remains unclear to date. Therefore, we investigated the stemness to determine the role of stem cells in nasal polyps, with additional analysis of the neuronal differentiation potential of nasal polyp cells. We determined gene and protein expression profiles of stem cells in nasal polyp tissues, using whole genome microarray, quantitative real-time PCR (qPCR), immunohistochemistry, and flow cytometry. To evaluate the neuronal differentiation potential of nasal polyp cells, we used an efficient xenogeneic co-culture model with unsliced adult rat brain biopsies, followed by qPCR, immunohistochemistry, and growth factor antibody arrays. During gene expression analysis and immunohistochemistry, we were able to detect different stem cell markers, like Oct-4, Sox2, Klf4, c-Myc, ABCG2, Nanog, CD133, and Nestin, which confirmed the existence of stem cell like cells within nasal polyps. In addition, co-culture experiments give evidence for a guided differentiation into the neuronal lineage by overexpression of Nestin, Neurofilament, and GM-CSF. Our study demonstrated the expression of stem cell-related markers in nasal polyps. Furthermore, we characterized, for the first time, the stemness and neuronal differentiation potential of nasal polyp cells. These results gave new insights into the pathogenesis of nasal polyps and its therapeutic effectiveness could represent a promising strategy in the future.
Assuntos
Autorrenovação Celular , Pólipos Nasais/imunologia , Rinite/imunologia , Sinusite/imunologia , Nicho de Células-Tronco/fisiologia , Células-Tronco/fisiologia , Adulto , Idoso , Animais , Diferenciação Celular , Linhagem da Célula , Células Cultivadas , Doença Crônica , Feminino , Fator Estimulador de Colônias de Granulócitos e Macrófagos/metabolismo , Humanos , Filamentos Intermediários/genética , Filamentos Intermediários/metabolismo , Fator 4 Semelhante a Kruppel , Masculino , Pessoa de Meia-Idade , Pólipos Nasais/diagnóstico , Nestina/genética , Nestina/metabolismo , Neurogênese , Fator 3 de Transcrição de Octâmero/metabolismo , Ratos , Ratos Sprague-Dawley , Rinite/diagnóstico , Sinusite/diagnóstico , TranscriptomaRESUMO
Keratin 16 (K16) is a cytoskeletal scaffolding protein highly expressed at pressure-bearing sites of the mammalian footpad. It can be induced in hyperproliferative states such as wound healing, inflammation and cancer. Here we show that the inactive rhomboid protease RHBDF2 (iRHOM2) regulates thickening of the footpad epidermis through its interaction with K16. K16 expression is absent in the thinned footpads of irhom2-/- mice compared with irhom2+/+mice, due to reduced keratinocyte proliferation. Gain-of-function mutations in iRHOM2 underlie Tylosis with oesophageal cancer (TOC), characterized by palmoplantar thickening, upregulate K16 with robust downregulation of its type II keratin binding partner, K6. By orchestrating the remodelling and turnover of K16, and uncoupling it from K6, iRHOM2 regulates the epithelial response to physical stress. These findings contribute to our understanding of the molecular mechanisms underlying hyperproliferation of the palmoplantar epidermis in both physiological and disease states, and how this 'stress' keratin is regulated.
Assuntos
Proteínas de Transporte/metabolismo , Epiderme/fisiologia , Queratina-16/metabolismo , Animais , Proteínas de Transporte/genética , Linhagem Celular , Proliferação de Células/fisiologia , Citoesqueleto/fisiologia , Regulação para Baixo , Células Epidérmicas , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patologia , Feminino , Fibroblastos , Mutação com Ganho de Função , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Queratina-6/metabolismo , Queratinócitos/fisiologia , Ceratodermia Palmar e Plantar/genética , Ceratodermia Palmar e Plantar/patologia , Masculino , Camundongos , Camundongos Knockout , Pressão , RNA Interferente Pequeno/metabolismo , Estresse Fisiológico/fisiologia , Técnicas de Cultura de Tecidos , Regulação para Cima , Cicatrização/fisiologiaRESUMO
IMPORTANCE OF THE FIELD: Cellular replacement therapies in vascular and urogenital organ disorders require an abundant source of smooth muscle cells. A promising approach would be the directed myogenic differentiation (characterized by the expression of alpha-smooth muscle actin (alpha-SMA)) into a sufficient amount of smooth muscle cells through easily obtainable adult stem cells, for example from the sweat gland. AREAS COVERED IN THIS REVIEW: We present novel multipotent adult stem cell populations derived from glandular tissues like pancreas, salivary gland and sweat gland and assess their myogenic potential. Their possible application in cell replacement therapies is discussed, with regard to numerous scaffold-based approaches in the course of the last decade. WHAT THE READER WILL GAIN: Multipotent glandular stem cells can be manipulated by different means to express a predominant smooth muscle-like phenotype. Possible promising applications of myogenic differentiated stem cells were evaluated, since several studies revealed the beneficial effect of somatic stem cells in replacement therapies for blood vessels, bladder reconstructions, etc. TAKE HOME MESSAGE: Glandular stem cells, especially sweat-gland-derived cells, provide an easily accessible and efficient source for autologous smooth muscle tissue, which might be used to replace vascular tissue in case of organ failure or disorder.