The role of EGFR signaling in autosomal dominant polycistic kidney disease (ADPKD)

Miedema A (2016) The role of EGFR signaling in autosomal dominant polycistic kidney disease (ADPKD). Master's Thesis / Essay, Biomedical Sciences.

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Abstract

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the most common heritable kidney disease affecting 3-4 in 10000 individuals. It is a proliferative renal disease characterized by the formation and growth of numerous cysts in both kidneys. ADPKD patients have a high likelihood of progression to renal failure for which dialysis is needed. As yet, there is no proven therapy available for clinical use. The proliferative abnormalities in ADPKD, that lead to cyst formation and growth, are potentially mediated via epidermal growth factor receptor (EGFR) signaling, which leads to increased cell proliferation. Since human studies in ADPKD regarding EGFR signaling are sparse, we examined the role of EGFR signaling in tissue of 19 ADPKD patients and compared the results to healthy controls with normal renal function We showed that the active, phosphorylated form of the EGFR (pEGFR) is expressed in distal tubules, collecting ducts, smooth muscle cells and in cyst lining epithelial cells in ADPKD patients. The pEGFR was expressed more strongly in ADPKD patients compared to controls with normal renal function, and apical mispolarization of the pEGFR was detected in ADPKD. This study implies that increased activity of the EGFR in ADPKD is mediated by its ligand HB-EGF, since we found co-localization of HB-EGF with pEGFR positive cysts. Furthermore, HB-EGF was strongly expressed in distal tubules and weakly expressed in proximal tubules. HB-EGF was expressed more strongly in ADPKD compared to controls with normal renal function. Moreover, in a previous study we found a positive correlation of urinary HB-EGF with ADPKD severity. Taken together, these studies imply that HB-EGF may be involved with disease progression in ADPKD, and as such is a potential candidate for therapy. Of note, research showed that HB-EGF was also upregulated in other chronic kidney diseases. Therefore, we hypothesize that HB-EGF may play a common role in kidney disease progression associated with increased inflammation, fibrosis and tissue repair. Targeting HB-EGF may therefore have a broad application in the field of nephrology.

Item Type:	Thesis (Master's Thesis / Essay)
Degree programme:	Biomedical Sciences
Thesis type:	Master's Thesis / Essay
Language:	English
Date Deposited:	15 Feb 2018 08:24
Last Modified:	15 Feb 2018 08:24
URI:	https://fse.studenttheses.ub.rug.nl/id/eprint/14475

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