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The effect of inhibition of EGFR transactivation in renal (patho)physiological processes

(2012) Mulder, Geertje Maaike

In this thesis the effect of inhibition of EGFR transactivation in renal (patho)physiological processes has been studied.
The EGFR is abundantly expressed in various cell types and plays a cardinal role in organ development, electrolyte homeostasis, and various other cellular processes, including survival, differentiation, migration and proliferation.
In the kidney, the EGFR and its ligands (growth factors that activate the EGFR by binding) contribute to the development of renal lesions. In disease conditions, the EGFR transactivation pathway may initially serve tissue repair, but may eventually be responsible for tissue fibrosis and functional deterioration.
In several experimental and human models the important role of the EGFR activation pathway in acute and chronic renal damage and magnesium handling has been shown. Inhibition of the EGFR and absence of one of the EGFR ligands have a protective effect on ischemia/reperfusion (/R) injury, an inevitable event during renal transplantation, shortly after I/R. In a nephrectomy model inhibition of the EGFR reduced the progression of hypertension and normalized cardiac function.
This thesis explored and emphasized the role of the EGFR transactivation pathway in renal physiology and pathophysiological processes. Inhibition of the EGFR activation pathway can be a suitable intervention therapy during and after renal transplantation and in the treatment of (cardiovascular complications in) renal diseases. New drugs that interfere in the EGFR activation pathway can possibly contribute to reducing the rejection risk following renal transplantation and be useful in the treatment of renal diseases.

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	Complete thesis

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ID	36736
Mother ID	36573
Order	mulder, g.m.
Name	g.m.mulder
Publish	yes
Embargo until	0000-01-01
OAI name	Dissertation
Path	faculties/medicine/2012/g.m.mulder/
Name Cover	vp.jpg
Created on:	2012-03-22 14:30:46
Last modified:	2013-02-15 14:28:01
Digital ID	4f6b379656249
Institute	Faculty of Medical Sciences
Place of publication	Groningen
Research institute	Graduate School for Drug Exploration (GUIDE)
Graduation date	2012-04-18
Date available	2012-04-19
Title	The effect of inhibition of EGFR transactivation in renal (patho)physiological processes
Title order	effect of inhibition of EGFR transactivation in renal (patho)physiological processes
Electronic	yes
Exchangeable	no
Printing on demand	yes
Export?	yes
Number of pages	182
Year issued	2012
Language	en
Type	Dissertation
Abstract NL	In dit proefschrift is het effect van remming van EGFR transactivatie op de fysiologische en pathofysiologische processen in de nier beschreven. De Epidermal Growth Factor Receptor (EGFR) is aanwezig op de celmembraan en speelt een rol in de ontwikkeling van organen, de elektrolythuishouding (magnesium) en diverse andere cellulaire processen zoals celdeling, differentiatie, migratie en overleving van cellen. In de nier komen de EGFR en zijn liganden (groeifactoren die via binding aan de EGFR betrokken zijn bij EGFR activatie) overvloedig tot expressie en dragen bij aan de ontwikkeling van nierschade. In eerste instantie kan de activatieroute van de EGFR betrokken zijn bij het herstellen van schade aan de nier, maar uiteindelijk kan het verantwoordelijk zijn voor fibrose en achteruitgang in het functioneren van de nier. In diverse experimentele en humane modellen is de belangrijke rol van de EGFR activatieroute in acute en chronische nierschade en magnesium huishouding aangetoond. Remming van de EGFR en afwezigheid van één de EGFR liganden hebben een beschermend effect op ischemie/reperfusie (I/R) schade, een onvermijdelijk proces tijdens een niertransplantatie, kort na I/R. In een nefrectomie model is de progressie van hypertensie geremd en hartfunctie genormaliseerd door remming van de EGFR. Dit proefschrift laat zien dat remming van de EGFR activatieroute mogelijk een geschikte therapie kan zijn bij een niertransplantatie en bij de behandeling van (cardiovasculaire complicaties in) nierziekten. Nieuwe medicijnen die kunnen ingrijpen op de EGFR activatieroute kunnen mogelijk bijdragen aan het verkleinen van de kans op afstoting na een niertransplantatie en aan de bestrijding van nierziekten.
Abstract EN	In this thesis the effect of inhibition of EGFR transactivation in renal (patho)physiological processes has been studied. The EGFR is abundantly expressed in various cell types and plays a cardinal role in organ development, electrolyte homeostasis, and various other cellular processes, including survival, differentiation, migration and proliferation. In the kidney, the EGFR and its ligands (growth factors that activate the EGFR by binding) contribute to the development of renal lesions. In disease conditions, the EGFR transactivation pathway may initially serve tissue repair, but may eventually be responsible for tissue fibrosis and functional deterioration. In several experimental and human models the important role of the EGFR activation pathway in acute and chronic renal damage and magnesium handling has been shown. Inhibition of the EGFR and absence of one of the EGFR ligands have a protective effect on ischemia/reperfusion (/R) injury, an inevitable event during renal transplantation, shortly after I/R. In a nephrectomy model inhibition of the EGFR reduced the progression of hypertension and normalized cardiac function. This thesis explored and emphasized the role of the EGFR transactivation pathway in renal physiology and pathophysiological processes. Inhibition of the EGFR activation pathway can be a suitable intervention therapy during and after renal transplantation and in the treatment of (cardiovascular complications in) renal diseases. New drugs that interfere in the EGFR activation pathway can possibly contribute to reducing the rejection risk following renal transplantation and be useful in the treatment of renal diseases.
Publisher	University of Groningen
Relation URI	http://www.rug.nl/
Rights	University of Groningen
PPN	34133815X
ISBN	9789036753692 (ISBN elektronische versie); 9789036753685 (ISBN gedrukte versie);
Subject GOO	Nierziekten; Epidermale $groeifactor; Tyrosine aminotransferase; Transplantatie; TGF; Inhibitie; Magnesium; Ischemie; Reperfusie; Proefschriften (vorm);
Subject NBC	urologie;
Author	Mulder, Geertje Maaike;
Author(s) name variant	Mulder, Gemma; Mulder, G.M.;
Tutors	Goor, H. van; Hillebrands, J.L.;

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The effect of inhibition of EGFR transactivation in renal (patho)physiological processes