Cilia structure and function defects in cystic fibrosis and related respiratory diseases

Abstract

The defects in cilia structure contributes to disease pathogenesis in cystic fibrosis, primary ciliary dyskinesia, and chronic obstructive pulmonary diseases. As a result of mutations in the genes responsible from mobile cilia structure, the microtubule structure is disrupted and protrusions and shrinkage occur in the cilium. These deformations cause loss of cilia function and decrease in ciliary beat frequency. This decrease disrupts the mucociliary clearance mechanism, which is called as the clearance mechanism of mucus from foreign microorganisms and bacteria in the airways. The macrophages and neutrophils migrating to the environment cause cytokine storm due to the inability of mucus to be cleared from the epithelial surface and the disease course exacerbates with the activation of inflammatory pathways. In this review, genes that have a function in mobile cilia formation and that show direct or indirect expression changes in cystic fibrosis, primary ciliary dyskinesia, and chronic obstructive pulmonary diseases are summarized. As a result of change in the expression of these genes, cell differentiation on the lung epithelial surface and lung pathophysiology are affected.

Keywords

• Respiratory diseases
• Cilia structure and function
• mucociliary clearance
• gene expression profile

Kistik Fibrozis ve Benzer Solunum Yolu Hastalıklarında Silya yapı ve İşlev Bozuklukları

Abstract

Hücre yüzeyinde bulunan siller; kistik fibrozis, primer siliyer diskinezi ve kronik obstrüktif akciğer hastalıklarında yapı ve işlev bozukluğuna uğrayarak hastalık patogenezinde önemli rol oynarlar. Sil oluşumu sırasında özellikle hareketli sil yapısını oluşturan genlerde görülen mutasyonlar sonucu silin mikrotübül yapısı bozulur ve sil yüzeyinde çıkıntılar ile büzülmeler meydana gelir ya da sil yapısı oluşamaz. Silde oluşan bu deformasyonlar sonucunda sil işlevinin kaybı gerçekleşmekte ve siliyer atım frekansında azalma görülmektedir. Bu azalış, mukusun havayollarındaki yabancı mikroorganizmalardan ve bakterilerden temizlenme mekanizması olarak adlandırılan mukosiliyer klirens mekanizmasını bozmaktadır. Mukusun epitel yüzeyden temizlenememesi, fazla üretilmesi ve kalınlaşması sebebiyle ortama göç eden makrofajlar ve nötrofiller sitokin fırtınasına neden olmakta, inflamatuar yolakların aktifleşmesiyle hastalık seyri ağırlaşmaktadır. Bu derlemede kistik fibrozis, primer siliyer diskinezi ve kronik obstrüktif akciğer hastalıklarında hareketli sil oluşumunda görev alan ve doğrudan ya da dolaylı olarak ifade değişimi gösteren genler ve işlevleri özetlenmiştir. İlişkili genlerin ifade değişimleri sonucunda akciğer epitel yüzeyindeki hücreler farklılaşarak akciğer patofizyolojisi etkilenmektedir.

Keywords

• Solunum yolu hastalıkları
• sil yapı ve işlevi
• mukosiliyer klirens
• gen ifade profili

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