New insights in the regulation of the epithelial magnesium channel in TRPM6 in kidney and intestine.

Abstract

The overall aim of the research presented in this thesis was to elucidate the molecular mechanisms of active Mg2+ (re)absorption, and therefore the maintenance of the Mg2+ balance in health and disease. This thesis described the identification of factors regulating TRPM6 and the discovery of EGF as an autocrine/paracrine hormone essential for maintenance of the body Mg2+ balance by regulating renal Mg2+ handling. Herewith, a major step is taken towards elucidation of the mechanisms which regulate Mg2+ homeostasis. Future studies directed to disclose the molecular mechanisms and (hormonal) factors that regulate transepithelial Mg2+ transport will certainly contribute to a better understanding of Mg2+ homeostasis. Increased knowledge of molecular and cellular aspects of Mg2+ homeostasis may lead to a better treatment of patients with Mg2+ deficiencies that is directed towards correcting the underlying functional defect(s). This will be of great benefit to patients because of the adverse symptoms resulting from hypomagnesemia, such as tetany, prolonged QT interval and cardiac arrhythmias. In addition, it might help to explain and provide new treatment strategies for unknown Mg2+ wasting disorders and its association with common chronic diseases such as cardiovascular diseases and diabetes.