title: The origin of interstitial myofibroblasts in chronic kidney disease.
abstract: Chronic kidney diseases (CKD), independent of their primary cause, lead to progressive, irreversible loss of functional renal parenchyma. Renal pathology in CKD is characterized by tubulointerstitial fibrosis with excessive matrix deposition produced by myofibroblasts. Because blocking the formation of these scar-forming cells represents a logical therapeutic target for patients with progressive fibrotic kidney disease, the origin of renal myofibroblasts is a subject of intense investigation. Although the traditional view holds that resident fibroblasts are the myofibroblast precursor, for the last 10 years, injured epithelial cells have been thought to directly contribute to the myofibroblast pool by the process of epithelial-to-mesenchymal transition (EMT). The recent application of genetic fate mapping techniques in mouse fibrosis models has provided new insights into the cell hierarchies in fibrotic kidney disease and results cast doubt on the concept that EMT is a source of myofibroblast recruitment in vivo, but rather point to the resident pericyte/perivascular fibroblast as the myofibroblast progenitor pool. This review will highlight recent findings arguing against EMT as a direct contributor to the kidney myofibroblast population and review the use of genetic fate mapping to elucidate the cellular mechanisms of kidney homeostasis and disease.
authors.affiliation: Renal Division, Brigham and Women's Hospital, Harvard Institutes of Medicine Rm 550, Boston, MA 02115, USA.
authors.forename: Ivica
authors.initials: I
authors.lastname: Grgic
authors.forename: Jeremy S
authors.initials: JS
authors.lastname: Duffield
authors.forename: Benjamin D
authors.initials: BD
authors.lastname: Humphreys
mesh_terms: D002908:Chronic Disease; D058750:Epithelial-Mesenchymal Transition; D005347:Fibroblasts / Q000502:physiology; D006801:Humans; D007668:Kidney / Q000473:pathology*; D007674:Kidney Diseases / Q000473:pathology*; D058628:Myofibroblasts / Q000502:physiology*; D013234:Stem Cells / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000502:physiology
chemical_list: D016212:Transforming Growth Factor beta