Current insight into kidney fibrosis and the role of EGFR as a potential therapeutic target

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Date

2023-02-17

Authors

Κουκουτσίδη, Παναγιώτα

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Abstract

The epidermal growth factor receptor (EGFR) is a member of the ErbB/HER family of receptors and its expression can be detected in almost every tissue of the human body. EGFR is a receptor tyrosine kinase with 11 known ligands. Over the years, researchers have conducted numerous experiments to determine the structure and the receptor’s potential implications in human physiology and pathophysiology. Renal fibrosis is the final common manifestation of a wide variety of chronic kidney diseases such as diabetic and obstructive nephropathy. Chronic kidney disease carries significant impact for the patients’ lives and its management poses a challenge for the physicians and the healthcare systems globally, especially due to its high prevalence. Τhis thesis presents a description of the normal ECM, the fibrotic process and its major mediators. Hereupon and based on the current literature, researchers argue that sustained or dysregulated activation of EGFR leads to renal fibrosis via the following mechanisms: a) activation and increased expression of TGF-β1, b) arrest of epithelial cells in the G2/M phase of cell cycle, and c) excessive production of cytokines and chemokines. Furthermore, the role of two EGFR ligands, amphiregulin and heparin-binding EGF, in the fibrotic process is explained. EGFR could be used as a therapeutic target for the treatment of chronic kidney disease. Nevertheless, extensive research has yet to be conducted to elucidate the exact molecular pathways implicated in EGFR activation. The aim of the thesis is to lay emphasis on the structural and functional complexity of the kidney and to explain the most prominent information about EGFR along with its role in chronic kidney disease. It also aims to highlight the absence of clinical trials that test specific anti EGFR agents as potential therapeutic agents for renal fibrosis. The interdisciplinary approach that was followed is essential for every scientist who wishes to dive into research and address elaborate clinical challenges.

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Keywords

Epidermal growth factor receptor (EGFR), Chronic Kidney Disease (CKD), Renal fibrosis, TGF-β

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