برهم کنش هلیکوباکتر پیلوری و اتوفاژی: یک مکانیسم محتمل درگیر در سرطانزایی معده
محورهای موضوعی : باکتری شناسی
مرضیه اسمعیل زاده
1
,
عباس یادگار
2
,
فرشید کفیل زاده
3
,
محمد کارگر
4
,
حمید اسدزاده عقدایی
5
1 - دانشجوی دکتری تخصصی، گروه میکروبیولوژی، واحد جهرم، دانشگاه آزاد اسلامی، جهرم، ایران
2 - استادیار، مرکز تحقیقات بیماری های منتقله از آب و غذا، پژوهشکده بیماری های گوارش و کبد، دانشگاه علوم پزشکی شهید بهشتی، تهران، ایران.
3 - استاد، گروه میکروبیولوژی، واحد جهرم، دانشگاه آزاد اسلامی، جهرم، ایران
4 - استاد، گروه میکروبیولوژی، واحد جهرم، دانشگاه آزاد اسلامی، جهرم، ایران
5 - استادیار، مرکز تحقیقات علوم پایه و اپیدمیولوژی بیماری های دستگاه گوارش،پژوهشکده بیماری های گوارش و کبد، دانشگاه علوم پزشکی شهید
کلید واژه: سرطان معده, هلیکوباکتر پیلوری, اتوفاژی, CagA, VacA,
چکیده مقاله :
هلیکوباکتر پیلوری یک باکتری گرم منفی است که در بافت معده بیش از نیمی از جمعیت جهان استقرار یافت می‌شود و اصلی‌ترین عامل خطر برای ایجاد سرطان معده است. هلیکوباکتر پیلوری به عنوان شایع‌ترین پاتوژن باکتریایی در انسان می‌باشد و ارتباط معناداری بین عفونت هلیکوباکتر پیلوری و سرطان معده وجود دارد. اتوفاژی یک فرآیند حفاظتی مورد استفاده توسط سلول‌های یوکاریوتی برای حفظ هوموستازی سلول و دفاع در برابر حمله میکروب‌های پاتوژن است. هلیکوباکتر پیلوری می‌تواند موجب القای فرایند اتوفاژی در سلول‌های اپیتلیال معده و فاگوسیت‌های حرفه‌ای همچون ماکروفاژ‌ها و سلول‌های دندریتیک شود. پروتین‌های بازدارنده تومور مانند فسفاتازها، هومولوگ تنسین، P53 و پروتین رتینوبلاستوما با اثر مثبت موجب تنظیم اتوفاژی می‌شوند، در مقابل ترکیبات انکوژن از قبیلBCL-2 و مسیرهای AKT/TOR نقش بازدارندگی در فرآیند اتوفاژی دارند. با این وجود، ارتباط بین تنظیم اتوفاژی و فرآیند تومورزایی همچنان ناشناخته است. در هنگام عفونت هلیکوباکتر پیلوری و پس از القای اتوفاژی، باکتری می‌تواند از طریق تنظیم کاهشی پروتین‌های اتوفاژی از این فرآیند فرار و یا این که باکتری از اتوفاگوزوم به عنوان محل مناسبی برای بقای داخل سلولی استفاده کند. همچنین، اتوفاژی می‌تواند منجر به بقای سلولی یا مرگ سلولی در هنگام سرطان معده شود. در نتیجه، نقش عفونت هلیکوباکتر پیلوری در القا و یا مهار فرآیند اتوفاژی و تاثیر آن بر مسیرهای مرتبط با سرطانزایی معده یک موضوع مورد بحث است که نیازمند مطالعات بیشتر به منظور درک برهم کنش‌های میکروب و اتوفاژی می‌باشد.
Helicobacter pylori is a Gram-negative bacterium that colonizes the gastric tissue of more than half of the world's population and is the major risk factor for the development of gastric cancer. H. pylori is the most common bacterial pathogen in humans, and there is a significant association between H. pylori infection and gastric cancer. Autophagy is a protective process used by eukaryotic cells to maintain cell homeostasis and defend against the attack of pathogenic microbes. H. pylori can induce autophagy in epithelial cells of the stomach and professional phagocytes such as macrophages and dendritic cells. Tumor inhibitory proteins including phosphatases, PTEN, P53, and retinoblastoma protein have a positive effect on autophagy regulation. In comparison, oncogenic products such as BCL-2 and AKT/TOR pathways play an inhibitory role on autophagy. However, the relationship between regulation of autophagy and tumorigenesis is still unclear. During H. pylori infection and after the induction of autophagy, the bacterium can escape this process by downregulation of autophagy-related proteins, and/or use the autophagosome as a suitable niche for intracellular survival. In addition, autophagy can cause cell survival or cell death through the gastric cancer process. In conclusion, the role of H. pylori infection in induction or inhibition of autophagy process, and its impact on gastric carcinogenic related pathways are a matter of controversy, which need further studies to understand the interactions between the microbe and autophagy.
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_||_
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Hepatology. 2021;18:613-29.
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Pathology. 2006;208:233-48.
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gastric malignancy. Physiological Reviews. 2010;90:831-58.
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Helicobacter pylori. Trends in Microbiology. 2010;18:479-86.
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genes. Developmental Cell. 2003;5:539-45.
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for diverse diseases. Nature Reviews Drug Discovery. 2012;11:709-30.
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37. Florey O, Overholtzer M. Autophagy proteins in macroendocytic engulfment. Trends in Cell
Biology. 2012;22:374-80.
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immune microenvironment. International Journal of Molecular Sciences. 2017;18:1566.
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the intracellular fate of Helicobacter pylori. Autophagy. 2013;9:639-52.
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Molecular Medicine. 2012;44:73-80.
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ageing kidneys. Nature Reviews Nephrology. 2014;11:34-45.
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