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.
MeSH terms
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Adipocytes / cytology
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Adipocytes / metabolism
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Animals
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Cell Differentiation
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Culture Media, Conditioned / chemistry
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Culture Media, Conditioned / pharmacology*
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Eye Proteins / genetics
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Eye Proteins / metabolism
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Female
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Gene Expression Regulation
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Granulins
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Hepatocyte Growth Factor / antagonists & inhibitors
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Hepatocyte Growth Factor / genetics*
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Hepatocyte Growth Factor / metabolism
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Homeodomain Proteins / genetics
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Homeodomain Proteins / metabolism
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Indoles / pharmacology
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Intercellular Signaling Peptides and Proteins / genetics
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Intercellular Signaling Peptides and Proteins / metabolism
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Intercellular Signaling Peptides and Proteins / pharmacology*
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Male
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Methylnitrosourea / pharmacology
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Mice
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Mice, Inbred C57BL
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Photoreceptor Cells, Vertebrate / cytology
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Photoreceptor Cells, Vertebrate / drug effects*
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Photoreceptor Cells, Vertebrate / metabolism
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Piperazines / pharmacology
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Primary Cell Culture
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Progranulins
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Regeneration / drug effects*
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Regeneration / genetics
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Retina / drug effects
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Retina / injuries
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Retina / metabolism
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Rhodopsin / genetics
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Rhodopsin / metabolism
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Signal Transduction
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Stem Cells / cytology
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Stem Cells / metabolism
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Sulfonamides / pharmacology
Substances
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((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)
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Culture Media, Conditioned
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Eye Proteins
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Granulins
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Grn protein, mouse
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HGF protein, mouse
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Homeodomain Proteins
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Indoles
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Intercellular Signaling Peptides and Proteins
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Piperazines
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Progranulins
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Rx protein, mouse
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Sulfonamides
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Hepatocyte Growth Factor
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Methylnitrosourea
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Rhodopsin