title: Diverse origins of the myofibroblast—implications for kidney fibrosis.
abstract: Fibrosis is the common end point of chronic kidney disease. The persistent production of inflammatory cytokines and growth factors leads to an ongoing process of extracellular matrix production that eventually disrupts the normal functioning of the organ. During fibrosis, the myofibroblast is commonly regarded as the predominant effector cell. Accumulating evidence has demonstrated a diverse origin of myofibroblasts in kidney fibrosis. Proposed major contributors of myofibroblasts include bone marrow-derived fibroblasts, tubular epithelial cells, endothelial cells, pericytes and interstitial fibroblasts; the published data, however, have not yet clearly defined the relative contribution of these different cellular sources. Myofibroblasts have been reported to originate from various sources, irrespective of the nature of the initial damage responsible for the induction of kidney fibrosis. Here, we review the possible relevance of the diversity of myofibroblast progenitors in kidney fibrosis and the implications for the development of novel therapeutic approaches. Specifically, we discuss the current status of preclinical and clinical antifibrotic therapy and describe targeting strategies that might help support resident and circulating cells to maintain or regain their original functional differentiation state. Such strategies might help these cells resist their transition to a myofibroblast phenotype to prevent, or even reverse, the fibrotic state.
authors.affiliation: Department of Pathology, University Medical Center Utrecht, H04.312, Heidelberglaan 100, 3584 CX, Utrecht, Netherlands.
authors.forename: Lucas L
authors.initials: LL
authors.lastname: Falke
authors.affiliation: Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Universiteitsweg 99, 3584 CG, Utrecht, Netherlands.
authors.forename: Shima
authors.initials: S
authors.lastname: Gholizadeh
authors.affiliation: Department of Pathology, University Medical Center Utrecht, H04.312, Heidelberglaan 100, 3584 CX, Utrecht, Netherlands.
authors.forename: Roel
authors.initials: R
authors.lastname: Goldschmeding
authors.affiliation: Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Universiteitsweg 99, 3584 CG, Utrecht, Netherlands.
authors.forename: Robbert J
authors.initials: RJ
authors.lastname: Kok
authors.affiliation: Department of Pathology, University Medical Center Utrecht, H04.312, Heidelberglaan 100, 3584 CX, Utrecht, Netherlands.
authors.forename: Tri Q
authors.initials: TQ
authors.lastname: Nguyen
mesh_terms: D002986:Clinical Trials as Topic; D005355:Fibrosis / Q000188:drug therapy / Q000209:etiology; D006801:Humans; D007668:Kidney / Q000473:pathology*; D007674:Kidney Diseases / Q000188:drug therapy / Q000209:etiology*; D058628:Myofibroblasts