title: Regulation of ciliary differentiation of human respiratory epithelial cells by the receptor for hyaluronan-mediated motility on hyaluronan-based biomaterials.
abstract: Selecting a scaffold that facilitates ciliary differentiation of respiratory epithelial cells (RECs) is crucial in developing tissue engineered respiratory epithelium. Hyaluronan derivative membranes, consisting of an esterified form of hyaluronan (HYAFF), have been proved to promote ciliary differentiation of RECs in the presence of retinoic acid (RA). However, the regulatory mechanism of ciliary differentiation-promoting effect of hyaluronan-based biomaterials remains unknown. In addition to investigating the ciliary differentiation of RECs on HYAFF with/without RA compared with that on collagen with/without RA, this study elucidates the role of the receptor for hyaluronan-mediated motility (RHAMM) in promoting ciliary differentiation of RECs. Analytical results of culturing RECs on collagen and HYAFF indicate that only HYAFF can increase the ciliary differentiation of RECs under RA-free conditions. The expression level of RHAMM mRNA of RECs more significantly decreases on collagen than that on HYAFF without RA. Therefore, by using lentiviral vector-based short hairpin RNA targeting RHAMM, the study further reveals that knockdown of RHAMM obviously inhibits the ciliary differentiation of RECs on collagen with RA and on HYAFF with/without RA. In addition to demonstrating that hyaluronan-based biomaterials partially "replace" RA in the ciliary differentiation of RECs, which is regulated by RHAMM, this study establishes that RHAMM regulates the ciliary differentiation-promoting effect of RA on RECs.
authors.affiliation: Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, Taipei 100, Taiwan.
authors.forename: Tsung-Wei
authors.initials: TW
authors.lastname: Huang
authors.forename: Po-Wen
authors.initials: PW
authors.lastname: Cheng
authors.forename: Yen-Hui
authors.initials: YH
authors.lastname: Chan
authors.forename: Te-Huei
authors.initials: TH
authors.lastname: Yeh
authors.forename: Yi-Ho
authors.initials: YH
authors.lastname: Young
authors.forename: Tai-Horng
authors.initials: TH
authors.lastname: Young
mesh_terms: D000107:Acetylation / Q000187:drug effects; D000199:Actins / Q000378:metabolism; D000818:Animals; D001672:Biocompatible Materials / Q000494:pharmacology*; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects*; D048430:Cell Shape / Q000187:drug effects; D002478:Cells, Cultured; D002923:Cilia / Q000187:drug effects / Q000378:metabolism*; D003094:Collagen / Q000494:pharmacology; D004847:Epithelial Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics / Q000378:metabolism; D006820:Hyaluronic Acid / Q000494:pharmacology*; D016086:Lentivirus / Q000235:genetics; D034622:RNA Interference / Q000187:drug effects; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D020545:Respiratory Mucosa / Q000166:cytology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014212:Tretinoin / Q000494:pharmacology; D014404:Tubulin / Q000378:metabolism
chemical_list: D000199:Actins; D001672:Biocompatible Materials; D016326:Extracellular Matrix Proteins; D018960:Hyaluronan Receptors; D034741:RNA, Small Interfering; D014404:Tubulin; C098946:hyaluronan-mediated motility receptor; D014212:Tretinoin; D006820:Hyaluronic Acid; D003094:Collagen