Nephrol Dial Transplant (2015) 0: 1–7 doi: 10.1093/ndt/gfv074 Full Review Discoidin domain receptor-1 and periostin: new players in chronic kidney disease Carlo Alfieri 1,2 , Panagiotis Kavvadas 1 , Paola Simonini 2 , Masami Ikehata 3 , Jean Claude Dussaule 1 , Christos E. Chadjichristos 1 , Maria Pia Rastaldi 3 , Piergiorgio Messa 2 and Christos Chatziantoniou 1 1 Institut National de la Santé et de la Recherche Médicale Research Unit S_1155, Bâtiment Recherche, Tenon Hospital, Paris, France, 2 Department of Medicine and Medical Specialties, Unit of Nephrology, Dialysis, and Renal Transplant, Fondazione Istituto di Ricerca e Cura a Carattere Scientifico Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy and 3 Research Laboratory of Nephrology, Fondazione Istituto di Ricerca e Cura a Carattere Scientifico Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy Correspondence and offprint requests to: Christos Chatziantoniou; E-mail: christos.chatziantoniou@upmc.fr ABSTRACT The incidence and prevalence of chronic kidney disease represents an important problem for public health. In renal diseases, the main histologic alterations derive from the development of renal fibrosis which results from the loss of the balance between pro- and anti-fibrotic factors. Tyrosine kinase receptors (RTKs) and matricellular proteins (MPs) are nowadays studied as potential modulators of renal injury. RTKs regulate cell cycle, migration, metabolism and cellular differentiation. Discoidin domain recep- tor-1 (DDR-1) is an RTK that has been extensively studied in cancer, and lung and renal diseases. It modulates inflammatory recruitment, extracellular matrix deposition and fibrosis; in renal diseases, it appears to act independently of the underlying disease. MPs regulate cell-matrix interactions and matrix accumulation, cellular adhesion and migration, and expression of inflammatory cells. Periostin is an MP, mainly studied in bone, heart, lung and cancer. Several studies demonstrated that it mediates cell- matrix interactions, migration of inflammatory cells and devel- opment of fibrosis. Recently, it has been reported in several ne- phropathies. In this review, we discuss the potential pathological roles of DDR-1 and periostin focussing on the kidney in both experimental models and human diseases. Keywords: discoidin domain receptor-1, matricellular proteins, periostin, renal fibrosis, tyrosine kinase receptors INTRODUCTION Chronic kidney disease (CKD) represents a major problem for public health. It affects up to 10% of the general population with a prevalence and incidence that has increased worldwide over the past 25 years and has almost doubled in both the USA and Europe [1]. Diabetes and high blood pressure are the major causes of CKD, followed by glomerulonephritis. Inde- pendent of the underlying cause, the pathogenesis of CKD is characterized by the progressive impairment of glomerular, tubulointerstitial and vascular compartments. Chronic expos- ure of these structures to pathogens leads to the development of glomerulosclerosis, interstitial fibrosis, tubular atrophy and vascular sclerosis. For CKD patients, dialysis and renal transplantation are the only effective therapies. Apart from drugs targeting the renin– angiotensin system (RAS), which are only partially effective, there are no drugs able to reduce or reverse fibrotic processes during kidney diseases. This review consists of three parts: in the first, recently pub- lished data about novel mediators of renal fibrosis are discussed; in the second and third ones, the role of tyrosine kinase recep- tors and matricellular proteins (MPs) in both renal and other diseases are briefly presented, focussing mainly on DDR-1 and periostin, respectively. © The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. 1 NDT Advance Access published March 31, 2015 by guest on February 9, 2016 http://ndt.oxfordjournals.org/ Downloaded from