Research Article: Epidermal growth factor and its influencing variables in healthy children and adults

Date Published: January 24, 2019

Publisher: Public Library of Science

Author(s): Sarang Meybosch, Amandine De Monie, Charlotte Anné, Luc Bruyndonckx, Angelika Jürgens, Benedicte Y. De Winter, Dominique Trouet, Kristien J. Ledeganck, Tatsuo Shimosawa.


Epidermal growth factor (EGF) stimulates cell proliferation and differentiation after binding to its receptor. Next to its role in magnesium homeostasis, EGF disturbances have been described in oncology, diabetes and autism spectrum disorders. The aim of this study was to determine EGF serum and urine values for both healthy children and adults. Next, we investigated the relation between several variables and urinary and serum EGF concentrations.

Both healthy adults (n = 50) and children (n = 78) were included. Serum and urinary EGF concentrations were measured with ELISA technology.

Serum EGF was inversely correlated with age (r = —0.873; p<0.001) and positively correlated with serum magnesium (r = 0.597; p<0.001). The urinary EGF was also inversely correlated with age (r = -0.855; p<0.001). In adults and children older than 13 years of age, the urinary EGF significantly differed between sexes (p = 0.001). Urinary EGF was positively correlated with serum magnesium (r = 0.583; p<0.001) and creatinine clearance (r = 0.524; p<0.001) and negatively correlated with the fractional excretion of magnesium (r = 0.248; p = 0.014). In a multivariate model, age and serum magnesium remained independently related to serum EGF while age, serum EGF and serum magnesium remained independently related to urinary EGF. This study provides valuable insights in urinary and serum EGF patterns in healthy subjects. By systematically correcting EGF for body surface, significant correlations with age, gender and magnesium were observed.

Partial Text

Human epidermal growth factor (EGF), a 6.000 molecular weight polypeptide, was first isolated by Cohen and Carpenter in 1975 [1]. EGF is a growth factor that stimulates cell growth, proliferation and differentiation by binding to its receptor EGFR [2]. It has been proven to be a potent mitogen by stimulating mRNA, DNA and protein synthesis of epithelial cells [3]. EGF is locally produced in several tissues, such as Henle’s loop and the distal convoluted tubule in the kidney, salivary glands and duodenum [4].

This clinical study provides new insights in serum and urinary EGF in children and adults. Firstly, age and length were significantly correlated with both serum and urinary EGF. We therefore propose to use body surface as a correction factor to determine EGF concentrations in children so that EGF values can be interpreted in both children and adults. Similarly, in other biological markers, such as creatinine clearance and cardiac index [29, 30], body surface is used as a correction factor. In children, the bedside Schwartz equation for creatinine clearance is based on serum creatinine and height and expressed as ml/min/1.73m2, thereby correcting for body surface [27]. Secondly, in this healthy population, serum EGF was independently related to serum magnesium concentrations. Interestingly, urinary EGF was not related to variables of the magnesium homeostasis.

The insides established in this study on healthy subjects, provide valuable knowledge for comparing and determining the role of EGF in many diseases, such as diabetes and autism spectrum disorder, as well as drug induced conditions. By systematically correcting EGF for body surface, significant correlations with age, gender starting from puberty on and magnesium were observed.




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