A carregar...
Publicação
Papel do CFTR nas doenças respiratórias : possibilidade de novas abordagens terapêuticas
| Nome: | Descrição: | Tamanho: | Formato: | |
|---|---|---|---|---|
| 847.08 KB | Adobe PDF |
Autores
Orientador(es)
Resumo(s)
O cystic fibrosis transmembrane conductance regulator (CFTR) é um transportador aniónico com um papel essencial na regulação da absorção e secreção de iões e água em tecidos epiteliais, nomeadamente nas vias aéreas. Nestas, o CFTR está envolvido na regulação de mecanismos de defesa essenciais, sendo crucial para a manutenção do líquido de superfície epitelial e de uma adequada clearence mucociliar. A fibrose quística (FQ) resulta da deficiência ou disfunção do CFTR determinada geneticamente. Evidências recentes sugerem que a disfunção do CFTR, determinada por mutações genéticas ou adquirida em proteínas CFTR wild type, pode ter um papel noutras doenças das vias respiratórias, como na doença pulmonar obstrutiva crónica (DPOC), na asma, na aspergilose broncopulmonar alérgica (ABPA), nas bronquiectasias difusas (DB), e na doença pulmonar associada a micobactérias não tuberculosas (PNTM). Mutações do gene do CFTR mesmo em apenas um alelo podem ter um papel fisiopatológico nas doenças referidas. Adicionalmente, fatores ambientais como a exposição ao fumo do tabaco, a álcool e a metais pesados, a hipóxia e acidose locais, o stress oxidativo e a inflamação, podem condicionar disfunção do CFTR wild type, com um potencial papel patogénico na DPOC, na asma, nas DB e na infeção PNTM, havendo igualmente evidência de correlação desta disfunção com o fenótipo clínico e gravidade da DPOC e, de forma menos clara, das DB e da ABPA. O desenvolvimento recente de novas abordagens terapêuticas direcionadas a corrigir a disfunção do CFTR na FQ permite considerar o recurso a terapêutica dirigida noutras doenças pulmonares com alterações da função do CFTR, nomeadamente utilizando, por exemplo, moduladores do CFTR, secretagagogos do cloro ou antagonistas da fosfodiesterase-4. Destaca-se a doença pulmonar obstrutiva crónica onde existe já evidência in vivo e in vitro da eficácia da terapêutica de substituição proteica.
The cystic fibrosis transmembrane conductance regulator (CFTR) is an anionic channel with an essential role in the regulation of the absorption and secretion of ions and water in the epithelial tissues, namely in the airways. In the airways, CFTR is involved in regulating the defence mechanisms, having a central role in keeping the airway surface liquid and an adequate mucociliary clearance. The Cystic Fibrosis (CF) results of the deficiency or malfunction of the CFTR genetically determined. Recent evidences suggest that CFTR dysfunction, genetically inherited or acquired in a wild type CFTR, may have a role in other airway diseases such as in chronic obstructive pulmonary disease (COPD), in asthma, in allergic bronchopulmonary aspergillosis (ABPA), in the diffuse bronchiectasis (DB) and in nontuberculous mycobacteria associated lung disease (PNTM). CFTR gene mutations even in only one allele may have a pathogenic role in the referred diseases. Additionally, environmental factors as exposure to cigarette smoke, alcohol, heavy metals, local hypoxia and acidosis, oxidative stress and inflammation may lead to wild type CFTR dysfunction, with a potential pathogenic role in COPD, in asthma, in DB and in PNTM. Moreover, there is also evidence that this dysfunction may correlate with the clinical phenotype and severity of COPD and, less clearly, of DB and ABPA. The recent development of CFTR targeted therapeutics for CF, leads to considering the use of that new therapeutic approaches targeted to correct CFTR dysfunction in other airway diseases, using, for example, CFTR modulators, Cl- secretagogues or phosphodiesterase 4 inhibitors. It is particularly relevant to mention that in COPD there is already evidence in vivo and in vitro of the efficacy of this targeted therapy.
The cystic fibrosis transmembrane conductance regulator (CFTR) is an anionic channel with an essential role in the regulation of the absorption and secretion of ions and water in the epithelial tissues, namely in the airways. In the airways, CFTR is involved in regulating the defence mechanisms, having a central role in keeping the airway surface liquid and an adequate mucociliary clearance. The Cystic Fibrosis (CF) results of the deficiency or malfunction of the CFTR genetically determined. Recent evidences suggest that CFTR dysfunction, genetically inherited or acquired in a wild type CFTR, may have a role in other airway diseases such as in chronic obstructive pulmonary disease (COPD), in asthma, in allergic bronchopulmonary aspergillosis (ABPA), in the diffuse bronchiectasis (DB) and in nontuberculous mycobacteria associated lung disease (PNTM). CFTR gene mutations even in only one allele may have a pathogenic role in the referred diseases. Additionally, environmental factors as exposure to cigarette smoke, alcohol, heavy metals, local hypoxia and acidosis, oxidative stress and inflammation may lead to wild type CFTR dysfunction, with a potential pathogenic role in COPD, in asthma, in DB and in PNTM. Moreover, there is also evidence that this dysfunction may correlate with the clinical phenotype and severity of COPD and, less clearly, of DB and ABPA. The recent development of CFTR targeted therapeutics for CF, leads to considering the use of that new therapeutic approaches targeted to correct CFTR dysfunction in other airway diseases, using, for example, CFTR modulators, Cl- secretagogues or phosphodiesterase 4 inhibitors. It is particularly relevant to mention that in COPD there is already evidence in vivo and in vitro of the efficacy of this targeted therapy.
Descrição
Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2017
Palavras-chave
Cystic fibrosis transmembrane conductance regulator Clearance de muco Bronquite crónica Bronquiectasias Pneumologia