Pulmoner Fibrozisin Moleküler Mekanizmaları
Özet
Pulmoner fibrozis (PF), alveolar epitel hasarı sonrası gelişen inflamasyon, fibroblast ve miyofibroblast artışı ile ekstrasellülar matriks (ECM) elemanlarının aşırı birikimi sonucu oluşan, akciğer parankiminin sertleşip skarlaşmasıyla karakterize ilerleyici bir hastalıktır. Bu durum akciğerin esnekliğini kaybettirerek gaz değişimini bozar ve solunum yetmezliğine yol açar. Genetik yatkınlığın yanı sıra çevresel faktörler, ilaçlar, enfeksiyonlar ve özellikle COVID-19 sonrası oluşan hasarlar hastalığı tetikler. Patogenezde inflamasyon ve oksidatif stres anahtar mekanizmalardır. Hasarla birlikte aktifleşen bağışıklık hücreleri; IL-1β, TGF-β ve TNF-α gibi sitokinleri salgılayarak fibrotik süreci ve epiteliyal mezenşimal transizyonu (EMT) uyarır. Artan reaktif oksijen türleri (ROS) ise doku hasarını, apoptozu ve anormal yara iyileşmesini tetikler. Hastalık araştırmalarında en yaygın hayvan modeli olarak DNA kırılması ve ROS üretimiyle fibrozis başlatan bleomisin kullanılmaktadır. PF'nin kesin bir tedavisi olmayıp, pirfenidon ve nintedanib gibi ajanlar yalnızca fonksiyonel düşüşü yavaşlatmaktadır; bu nedenle hücresel ve moleküler mekanizmaların aydınlatılması hayati önem taşımaktadır.
Pulmonary fibrosis (PF) is a progressive lung disease characterized by inflammation, an increase in fibroblasts and myofibroblasts, and excessive accumulation of extracellular matrix (ECM) components following alveolar epithelial damage, leading to the hardening and scarring of the lung parenchyma. This condition causes the lungs to lose their elasticity, disrupting gas exchange and resulting in respiratory failure. In addition to genetic predisposition, environmental factors, medications, infections, and particularly post-COVID-19 damage trigger the disease. Inflammation and oxidative stress are key mechanisms in pathogenesis. Immune cells activated by injury release cytokines such as IL-1β, TGF-β, and TNF-α, stimulating the fibrotic process and epithelial-mesenchymal transition (EMT). Increased reactive oxygen species (ROS) trigger tissue damage, apoptosis, and abnormal wound healing. Bleomycin, which induces fibrosis through DNA cleavage and ROS production, is the most common animal model used in research. There is no definitive cure for PF, and agents like pirfenidone and nintedanib only slow down functional decline; thus, elucidating cellular and molecular mechanisms is of vital importance.
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