Investigating the Role of PI4KA in Angiogenesis

الموضوعات

طب

الملخص

Angiogenesis, the formation of new blood vessels, is a critical cellular process towards establishing a functional circulatory system capable of delivering oxygen and nutrients to tissues. Abnormal angiogenesis regulation leads to defects in a vascular network structure that could contribute to the pathogenesis of diseases such as ischemic vascular disease, diabetes, and cancer. Angiogenesis is a multistep cellular process including sprouting initiation, tubulogenesis, branching, lumen formation and vascular stabilization. PI4KA, a lipid kinase, produces the primary source of the PI4P content of plasma membrane that converts into the signalling lipids PI(4,5)P2 and PI(3,4,5)P3. Both signalling lipids are vital for many cell functions, including cell growth, endocytosis, metabolism, ion channel regulation and cell motility. However, the role of PI4KA in endothelial cell biology and angiogenesis remains unknown. The current study aimed to investigate the role of PI4KA in angiogenesis using the siRNA knockdown approach in combination with relevant phenotypic cell-based assays. We showed that PI4KA knockdown by siRNA inhibits endothelial tubulogenesis as assessed by two in vitro angiogenesis assays. In addition, we found that PI4KA inhibition led to decrease endothelial cell migration and proliferation, which are essential for angiogenesis. Single-cell morphology analysis demonstrated that PI4KA downregulated endothelial cells increased their size and width-to-length ratio. In contrast, the actin content is decreased when PI4KA knockdown cells are grown under high density. Using 39 phospho-kinase antibody array, we found that PI4KA inhibition led to decreased phosphorylation of several kinases involved in angiogenesis, including ERK, EGFR and PDGFR. In conclusion, our findings suggest that PI4KA is required for proper endothelial tube formation and open an avenue for potential therapeutic targeting of PI4KA as an anti-cancer therapy by controlling tumor angiogenesis.

روابط وملفات

التعريف والنوع

رقم الوثيقة

0374c0e2-e0ee-4f8a-97e1-ded1e4af4301

رقم العقد

0

نوع الوسائط

Crawler

نوع المحتوى

الرسائل العلمية

صيغة المصدر

رسائل ماجيستير

نوع الملف

pdf text

أسماء الملفات

0374c0e2-e0ee-4f8a-97e1-ded1e4af4301_1.pdf

بيانات النشر

ألقاب المؤلفين

[{"name_ar":"Ayman Al Haj Zen","title_ar":"اشراف","title_en":"Supervision"},{"name_ar":"Hend Ghassan Ismail Roshdi","title_ar":"اعداد","title_en":"Preparation"}]

اللغة

English

المصدر والدورية

اسم المصدر

Investigating the Role of PI4KA in Angiogenesis

المحتوى والصفحات

عدد الصفحات

0

كلمات الباحثين

Blood vessels - Tubulogenesis - Angiogenesis - Cell growth

إشراف وإعداد

الإشراف

Ayman Al Haj Zen

الإعداد

Hend Ghassan Ismail Roshdi

الاقتباسات الببليوغرافية