مروری کلی بر مسیرهای تنظیمی احساس اکسیژن محیطی و ریزمحیطی توسط عوامل القا شده به ‌وسیله‌ی هیپوکسی (HIF)

نوع مقاله : مقاله مروری

نویسندگان

1 مرکز تحقیقات ژنتیک انسانی، دانشگاه علوم پزشکی بقیه‌اله (عج)، تهران، ایران

2 دکتری تخصصی بیوشیمی، مرکز تحقیقات نانوبیوتکنولوژی، دانشگاه علوم پزشکی بقیه‌اله (عج)، تهران، ایران

3 استاد، مرکز تحقیقات ژنتیک انسانی، دانشگاه علوم پزشکی بقیه‌اله (عج)، تهران، ایران

چکیده

کمبود اکسیژن یا هیپوکسی، می‌تواند کمبود اکسیژن محیط بیرون از بدن (حس شده توسط سلول‌های ریوی) یا کمبود اکسیژن ریزمحیط‌های درونی بدن (حس شده توسط سایر سلول‌های بدن همچون سلول‌های سرطانی) را شامل گردد. پاسخ سلولی به نوسانات اکسیژن به ‌طور عمده توسط عوامل القا شده به ‌وسیله‌ی هیپوکسی (Hypoxia-inducible factors یا HIFs) میانجی‌گری می‌شوند. به طور کلی، اولین اندام که بعد از هر دم که باعث دمیدن اکسیژن محیط به داخل و تماس با آن می‌شود، ریه می‌باشد. با این وجود، هنوز مسیرهای تنفسی شناخته‌ شده‌ی Hif برای احساس اکسیژن محیطی در ریه بسیار محدود است. از این رو، در این مقاله‌ی مروری، ابتدا نقش ایزوفرم‌های HIF1 و HIF2 در عروق و برونش‌های ریوی (مشتمل بر سلول‌های عضله‌ی صاف و اندوتلیال عروق و سلول‌های اپی‌تلیال برونشیال ریوی) و پاسخ‌های آن به ناکافی بودن اکسیژن محیطی مورد بررسی قرار می‌گیرد. سپس، به بررسی نقش HIF در احساس اکسیژن ریزمحیطی (داخلی) در سلول‌ها و بافت‌های غیر ریوی همراه با کلیه‌ی مکانیزم‌های مولکولی درگیر در آن سلول و بافت‌ها پرداخته می‌شود. آن گاه، از بین کلیه‌ی سلول‌های درگیر در مسیرهای احساس اکسیژن ریزمحیطی، به طور ویژه‌ای به تومورها و سلول‌های سرطانی و سلول‌های بنیادی سرطانی و نقش دقیق‌تر مولکول HIF در این سلول‌ها و بافت‌ها اشاره می‌گردد.

کلیدواژه‌ها


عنوان مقاله [English]

A Comprehensive Review on Environmental and Microenvironmental Oxygen Sensing Pathways Mediated by Hypoxia-Inducible Factors (HIFs)

نویسندگان [English]

  • Fatemeh Choopani 1
  • Ali Choopani 2
  • Mahmood Tavallaei 3
  • Nasrin Kariminejad 1
1 Human Genetics Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran
2 PhD in Biochemistry, Applied Biotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran
3 Professor, Human Genetics Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran
چکیده [English]

Oxygen deficiency, referred to as hypoxia, can be divided into two categories of environmental (exogenous) which is sensitized by respiratory cells, and microenvironmental (endogenous) responses by other cells in the body, like cancer cells. Cell responses to oxygen fluctuations are mediated by hypoxia-inducible factors (HIFs). Lung is known as the first organ that encounters the exogenous and environmental oxygen after breathing. However, data are limited for HIF respiratory pathways of environmental oxygen sensing inside the lung cells. Thus, we evaluated the role of both HIF-1 and HIF-2 isoforms in environmental hypoxia sensation by pulmonary vascular and bronchial cells. Then, we introduced the role of HIFs in microenvironmental and endogenous oxygen sensation in tissues and cells other than respiratory cells as well as all of involved molecular mechanisms in those non-lung cells and tissues. Next, a detailed emphasize was put on the strict role of HIF molecule in tumor cells and cancer stem cells.

کلیدواژه‌ها [English]

  • Hypoxia
  • Hypoxia-inducible factor 1
  • Hypoxia-inducible factor 2
  • Lung
  • Cancer
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