بررسی عملکرد miRNA در بیماری سیستیک فیبروزیس

نوع مقاله : مقاله مروری

نویسندگان

1 دانشیار، مرکز تحقیقات بیماری‌های تنفسی اطفال، پژوهشکده‌ی سل و بیماری‌های ریوی، مرکز آموزشی، پژوهشی و درمانی سل و بیماری‌های ریوی بیمارستان دکتر مسیح دانشوری، دانشگاه علوم پزشکی شهید بهشتی، تهران، ایران

2 استادیار، مرکز تحقیقات مایکوباکتریولوژی، پژوهشکده‌ی سل و بیماری‌های ریوی، مرکز آموزشی، پژوهشی و درمانی سل و بیماری‌های ریوی بیمارستان دکتر مسیح دانشوری، دانشگاه علوم پزشکی شهید بهشتی، تهران، ایران

3 استاد، مرکز تحقیقات مایکوباکتریولوژی، پژوهشکده‌ی سل و بیماری‌های ریوی، مرکز آموزشی، پژوهشی و درمانی سل و بیماری‌های ریوی بیمارستان دکتر مسیح دانشوری، دانشگاه علوم پزشکی شهید بهشتی، تهران، ایران

چکیده

سیستیک فیبروزیس (Cystic fibrosis یا CF) نوعی اختلال اتوزومی مغلوب است که به علت جهش‌هایی در ژن تنظیم کننده‌ی رسانایی میان غشایی سیستیک فیبروزیس (Cystic fibrosis transmembrane conductance regulator یا CFTR) ایجاد می‌شود. عدم تنظیم miRNA در بسیاری از بیماری‌های ریوی نظیر CF گزارش شده است. کاهش یا افزایش سطح miRNA اثرات مهمی بر پاسخ‌های ایمنی ذاتی در مسیر تنفسی CF دارد، مانند اختلال در عملکرد پاسخ التهابی ایجاد شده به واسطه‌ی نوتروفیل‌ها و ماکروفاژها و نیز التهاب مزمن که باعث تخریب و فیبروز بافت ریه در بیماران مبتلا به CF می‌شود. وجود یک نشانگر زیستی اختصاصی برای تشخیص پیشرفت بیماری ریوی، بررسی التهاب و عملکرد سلولی می‌تواند گزینه‌ی مناسبی برای تشخیص CF باشد. برای مثال، miRNAهای موجود در خلط، می‌توانند جهت بررسی عملکرد ریوی، بسیار ایده‌آل باشند. در حال حاضر، از miRNA در درمان یا تشخیص بالینی CF استفاده نمی‌شود، اما مطالعات زیادی miRNAها را به عنوان نشانگرهای زیستی بالقوه برای این بیماری بیان می‌کنند. این مطالعات، پیشنهاد می‌کنند که درمان‌های بر پایه‌ی miRNA که باعث افزایش بیان CFTR می‌شوند، می‌توانند گزینه‌ی بسیار مناسبی برای تنظیم میزان CFTR در آزمایش‌های بالینی بر روی بیماران CF باشند. در این مقاله‌ی مروری، پس از تشریح گروه‌های مختلف miRNA و مکانیسم عملکرد آن جهت تنظیم بیان پروتئین، مطالعات گوناگون مرتبط با miRNA در سیستیک فیبروزیس بررسی گردید. همچنین، امکان به کارگیری miRNA به عنوان نشانگر زیستی در بیماری سیستیک فیبروزیس و نقش آن در روش‌های درمانی مختلف بر پایه‌ی miRNA مورد بحث قرار گرفته است.

کلیدواژه‌ها

عنوان مقاله [English]

Investigation of miRNA Functionality in Cystic Fibrosis

نویسندگان [English]

  • Maryam Hassanzad 1
  • Jalaledin Ghanavi 2
  • Ali Akbar Velayati 3
1 Associate Professor, Pediatric Respiratory Diseases Research Center (PRDRC), National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
2 Assistant Professor, Mycobacteriology Research Center (MRC), National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
3 Professor, Mycobacteriology Research Center (MRC), National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
چکیده [English]

Cystic fibrosis (CF) is an autosomal recessive disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The irregularities in miRNA expression have been reported in many pulmonary diseases, including CF. An increase or a decrease in miRNA levels has important influences on innate immune responses in respiratory tract of the patients with CF, such as impaired function of the inflammatory responses caused by neutrophils and macrophages, as well as chronic inflammation, which can lead to degradation and fibrosis of the lung tissue in these patients. The presence of a specific biomarker for diagnosis of pulmonary disease, inflammation, and cellular function can be a good candidate for diagnosis of CF. For example, sputum miRNAs can be ideal for checking pulmonary function. Although miRNA is not currently used for treatment or clinical diagnosis of CF, many studies have suggested miRNAs as potential biomarkers for the disease. miRNA-based treatments, that enhance the expression of CFTR, can be a very suitable option for adjusting CFTR levels in clinical trials on patients with CF. In this review article, after describing different miRNA groups, and its mechanism of action for regulation of protein expression, various studies related to miRNA in CF were investigated. In addition, the possibility to apply miRNA as a biomarker in CF, and its role in different miRNA-based therapeutic approaches were discussed.

کلیدواژه‌ها [English]

  • Cystic fibrosis
  • Lung
  • miRNA

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مجله دانشکده پزشکی اصفهان
دوره 37، شماره 532 - شماره پیاپی 532
مرداد و شهریور 1398
صفحه 736-746

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  • تاریخ دریافت: 08 مرداد 1398
  • تاریخ بازنگری: 31 فروردین 1403
  • تاریخ پذیرش: 17 فروردین 1401

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