Translational Nephrology The great escape—myofibroblasts in fibrosis and the immune system∗

The extent of renal interstitial fibrosis is one of the most important prognostic factors in kidney biopsies and is a key component of almost every form of progressive renal failure [1]. Similarly, fibrosis is also a morphological correlate of progressive organ failure in liver, lung and heart. In all organs, fibrosis is the result of a process called fibrogenesis in which myofibroblasts (the name is due to the de novo expression of α-smooth muscle actin in these cells whose expression is normally restricted to vascular smooth muscle cells) are the key effector cells [2]. Myofibroblasts are formed via an intermediate form entitled the ‘protomyofibroblast ’ characterized by the acquisition of contractile stress fibres [3]. In the kidney, myofibroblasts are derived mainly from activation of resident interstitial fibroblasts, albeit differentiation processes of periadventitial cells, mesenchymal stem cells or tubular epithelial cells may play a role as well [4]. Thus, myofibroblasts may have several precursors, and similar mechanisms of myofibroblast formation have been described in the liver [5] and lung [6]. However, it should be appreciated that not all matrix-synthesizing cells are myofibroblasts and vice versa that not all myofibroblasts contribute to interstitial matrix deposition pointing to a certain degree of heterogeneity of these cells [3]. Myofibroblasts and the immune system Myofibroblasts play a critical role in the resolution of in-flammation and scar formation. Whereas initial stimulation and proliferation of these cells helps in confining inflamma