MEK1 Required for Invasive Growth of mIMCD3 renal Cells in a 3D Collagen Matrix

Abstract

Branching morphogenesis is an essential process during kidney development: This process controls epithelialization of the metanephric mesenchyme during the induction of branching structures and in this way determines the number of nephrons. Various grow factors, such HGF, have been implicated in branching morphogenesis in renal cells, including mIMCD3 ( murine inner medullary collecting duct) and MDCK cells. Growth factors which induce branching morphogenesis in renal cells also activate the MEK1/ERK pathway. The authors analyzed the potential role that this pathway might play in branching morphogenesis. The authors show that PD98059, a specific inhibitor of MEK1,inhibits branching of mIMCD3 cells. Adenoviral-driven expression of the activated form of MEK1, Ad-MEK1-DD, in mIMCD3 cells, results in the induction of branching structures, whereas non-infected IMCD3 cells exhibit little or no branching. Furthermore, teh authors show that Stat3 is not activated in branching mIMCD3 cells.Presented data show that activation of the MEK1/ERK pathway is necessary for the induction of branching in mIMCD3 renal cells, indipendent of Stat3 activation.