Mitogen activated protein kinase signaling in the kidney: Target for intervention?

Mitogen activated protein kinases (MAPKs) are intracellular signal transduction molecules, which connect cell-surface receptor signals to intracellular processes. MAPKs regulate a range of cellular activities including cell proliferation, gene expression, apoptosis, cell differentiation and cytokine production. The MAPK superfamily consists of at least four families: extracellular signal-regulated kinase (ERK), p38 MAPK, Jun-NH2-terminal kinase (JNK), and ERK5. Each of these families exerts particular downstream effects, although interactions have been described. MAPK activity is present in the normal kidney. Moreover, in various types of renal disease, renal MAPK expression is increased. Interventions that provide renoprotection, such as ACE-inhibition or statin therapy, may reduce renal MAPK expression, suggesting that increased renal MAPK expression is involved in the pathophysiology of renal damage. Studies using specific MAPK inhibitors have been used to further elucidate this role. This review gives an overview of available in vitro data on MAPK activation (focussed on renal cell types), and describes MAPK localization and possible functions in the normal and diseased kidney in man, and in experimental renal disease. Studies reporting the effect of conventional renoprotective intervention on renal MAPK expression are reviewed, as well as the available data on specific MAPK inhibition, both in the clinical and experimental setting. The available data appear to support the potential of MAPK inhibition as a novel intervention strategy in renal disease, but future clinical studies are needed to substantiate this assumption, and to establish its safety. (copyright) 2006 Wiley-VCH Verlag GmbH & Co. KGa