title: Corneal endothelial cell fate is maintained by LGR5 through the regulation of hedgehog and Wnt pathway.
abstract: Leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5), a target of Wnt signaling, is reportedly a marker of intestine, stomach, and hair follicle stem cells in mice. To gain a novel insight into the role of LGR5 in human corneal tissue, we performed gain- and loss-of-function studies. The findings of this study show for the first time that LGR5 is uniquely expressed in the peripheral region of human corneal endothelial cells (CECs) and that LGR5((+)) cells have some stem/progenitor cell characteristics, and that in human corneal endothelium, LGR5 is the target molecule and negative feedback regulator of the Hedgehog (HH) signaling pathway. Interestingly, the findings of this study show that persistent LGR5 expression maintained endothelial cell phenotypes and inhibited mesenchymal transformation (MT) through the Wnt pathway. Moreover, R-spondin-1, an LGR5 ligand, dramatically accelerated CEC proliferation and also inhibited MT through the Wnt pathway. These findings provide new insights into the underlying homeostatic regulation of human corneal endothelial stem/progenitor cells by LGR5 through the HH and Wnt pathways.
authors.affiliation: Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Kana
authors.initials: K
authors.lastname: Hirata-Tominaga
authors.forename: Takahiro
authors.initials: T
authors.lastname: Nakamura
authors.forename: Naoki
authors.initials: N
authors.lastname: Okumura
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kawasaki
authors.forename: Eunduck P
authors.initials: EP
authors.lastname: Kay
authors.forename: Yann
authors.initials: Y
authors.lastname: Barrandon
authors.forename: Noriko
authors.initials: N
authors.lastname: Koizumi
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kinoshita
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D004728:Endothelium, Corneal / Q000166:cytology* / Q000378:metabolism; D053823:Hedgehog Proteins / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008252:Macaca fascicularis; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D015398:Signal Transduction; D060449:Wnt Signaling Pathway / Q000502:physiology*
chemical_list: D053823:Hedgehog Proteins; C116884:LGR5 protein, human; D043562:Receptors, G-Protein-Coupled
keywords: Cornea; Endothelium; Hedgehog; LGR5; Stem cell; Wnt