title: Hyaluronan's Role in Fibrosis: A Pathogenic Factor or a Passive Player?
abstract: Fibrosis is a debilitating condition that can lead to impairment of the affected organ's function. Excessive deposition of extracellular matrix (ECM) molecules is characteristic of most fibrotic tissues. Fibroblasts activated by cytokines or growth factors differentiate into myofibroblasts that drive fibrosis by depositing ECM molecules, such as collagen, fibronectin, and connective tissue growth factor. Transforming growth factor-β (TGF-β) is one of the major profibrotic cytokines which promotes fibrosis by signaling abnormal ECM regulation. Hyaluronan (HA) is a major ECM glycosaminoglycan that is regulated by TGF-β and whose role in fibrosis is emerging. Aside from its role as a hydrating, space filling polymer, HA regulates different cellular functions and is known to have a role in wound healing and inflammation. Importantly, HA deposition is increased in multiple fibrotic diseases. In this review we highlight studies that link HA to fibrosis and discuss what is known about the role of HA, its receptors, and its anabolic and catabolic enzymes in different fibrotic diseases.
authors.affiliation: Department of Pathobiology, Cleveland Clinic Lerner Research Institute, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
authors.forename: Sami
authors.initials: S
authors.lastname: Albeiroti
authors.affiliation: Department of Pathobiology, Cleveland Clinic Lerner Research Institute, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
authors.forename: Artin
authors.initials: A
authors.lastname: Soroosh
authors.affiliation: Department of Pathobiology, Cleveland Clinic Lerner Research Institute, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
authors.forename: Carol A
authors.initials: CA
authors.lastname: de la Motte
mesh_terms: D000199:Actins / Q000378:metabolism; D003094:Collagen / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism* / Q000473:pathology; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D005355:Fibrosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D006820:Hyaluronic Acid / Q000378:metabolism*; D058628:Myofibroblasts / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism
chemical_list: D000199:Actins; D053773:Transforming Growth Factor beta1; D006820:Hyaluronic Acid; D003094:Collagen