title: Progranulin promotes the retinal precursor cell proliferation and the photoreceptor differentiation in the mouse retina.
abstract: Progranulin (PGRN) is a secreted growth factor associated with embryo development, tissue repair, and inflammation. In a previous study, we showed that adipose-derived stem cell-conditioned medium (ASC-CM) is rich in PGRN. In the present study, we investigated whether PGRN is associated with retinal regeneration in the mammalian retina. We evaluated the effect of ASC-CM using the N-methyl-N-nitrosourea-induced retinal damage model in mice. ASC-CM promoted the differentiation of photoreceptor cells following retinal damage. PGRN increased the number of BrdU(+) cells in the outer nuclear layer following retinal damage some of which were Rx (retinal precursor cell marker) positive. PGRN also increased the number of rhodopsin(+) photoreceptor cells in primary retinal cell cultures. SU11274, a hepatocyte growth factor (HGF) receptor inhibitor, attenuated the increase. These findings suggest that PGRN may affect the differentiation of retinal precursor cells to photoreceptor cells through the HGF receptor signaling pathway.
authors.affiliation: Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Kuse
authors.affiliation: Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Tsuruma
authors.affiliation: Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan.
authors.forename: Sou
authors.initials: S
authors.lastname: Sugitani
authors.affiliation: Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Izawa
authors.affiliation: Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan.
authors.forename: Yuta
authors.initials: Y
authors.lastname: Ohno
authors.affiliation: Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan.
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Shimazawa
authors.affiliation: Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Hara
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation; D017077:Culture Media, Conditioned / Q000737:chemistry / Q000494:pharmacology*; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D000077155:Granulins; D017228:Hepatocyte Growth Factor / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D007211:Indoles / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D008770:Methylnitrosourea / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D020419:Photoreceptor Cells, Vertebrate / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology; D061251:Primary Cell Culture; D000077153:Progranulins; D012038:Regeneration / Q000187:drug effects* / Q000235:genetics; D012160:Retina / Q000187:drug effects / Q000293:injuries / Q000378:metabolism; D012243:Rhodopsin / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: C478479:((3Z)-N-(3-chlorophenyl)-3-((3,5-dimethyl-4-((4-methylpiperazin-1-yl)carbonyl)-1H-pyrrol-2-yl)methylene)-N-methyl-2-oxo-2,3-dihydro-1H-indole-5-sulfonamide); D017077:Culture Media, Conditioned; D005136:Eye Proteins; D000077155:Granulins; C120204:Grn protein, mouse; C553307:HGF protein, mouse; D018398:Homeodomain Proteins; D007211:Indoles; D036341:Intercellular Signaling Peptides and Proteins; D010879:Piperazines; D000077153:Progranulins; C501274:Rx protein, mouse; D013449:Sulfonamides; D017228:Hepatocyte Growth Factor; D008770:Methylnitrosourea; D012243:Rhodopsin