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Importin 13 serves as a potential marker for corneal epithelial progenitor cells.

ABSTRACT: Importin13 (IPO13), the newest member of importin-beta family discovered recently, is a unique nucleus-cytoplasm bidirectional transport receptor protein. In this study, IPO13 expression in human corneal tissue, limbal epithelial primary explant and clonal culture was evaluated by immunostaining and reverse-transcription polymerase chain reasgon. IPO13 function was evaluated in the corneal epithelial culture treated with IPO13 inhibitor, or fetal bovine serum (FBS)-containing Dulbecco's modified Eagle's medium (DMEM) medium by colony-forming efficiency, clone growth capacity, MTT, immunostaining, and Western blotting assay. IPO13 protein was expressed mainly in nuclei of limbal epithelial basal cells, but not in the other cell layers of limbus and full thickness of corneal epithelia. IPO13 was expressed in the majority of epithelial cells in early-stage clones and in the margin of late-stage clones. IPO13 was positively expressed in mouse TKE2 progenitor cells cultured in keratinocyte serum-free defined medium, while it became negative in FBS-containing DMEM, which promoted TKE2 cell differentiation. In the presence of IPO13 inhibitor, IPO13 expression and the proliferative capacity decreased in human limbal epithelial clones and mouse TKE2 cells, which were accompanied with the cell differentiation. In conclusion, our findings demonstrate for the first time that IPO13 is uniquely expressed by human limbal basal epithelial cells, and plays an important role in maintaining the phenotype, high proliferative potential, and less differentiation of corneal epithelial progenitor cells, suggesting that IPO13 could serve as a novel potential marker for corneal epithelial progenitor cells.

SUBMITTER: Wang H

PROVIDER: S-EPMC2846104 | biostudies-literature | 2009 Oct

REPOSITORIES: biostudies-literature

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Importin 13 serves as a potential marker for corneal epithelial progenitor cells.

Wang Hua H Tao Tao T Tang Jing J Mao Yi-Hui YH Li Wei W Peng Juan J Tan Gang G Zhou Yue-Ping YP Zhong Jing-Xiang JX Tseng Scheffer C G SC Kawakita Tetsuya T Zhao Yong-Xiang YX Liu Zu-Guo ZG

Stem cells (Dayton, Ohio) 20091001 10

Importin13 (IPO13), the newest member of importin-beta family discovered recently, is a unique nucleus-cytoplasm bidirectional transport receptor protein. In this study, IPO13 expression in human corneal tissue, limbal epithelial primary explant and clonal culture was evaluated by immunostaining and reverse-transcription polymerase chain reasgon. IPO13 function was evaluated in the corneal epithelial culture treated with IPO13 inhibitor, or fetal bovine serum (FBS)-containing Dulbecco's modified ...[more]

PMID: 19593795

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Project description:In idiopathic pulmonary fibrosis loss of alveolar epithelium induces inflammation of the pulmonary tissue followed by accumulation of pathogenic myofibroblasts leading eventually to respiratory failures. In animal models inflammatory and resident cells have been demonstrated to contribute to pulmonary fibrosis. Regenerative potential of pulmonary and extra-pulmonary stem and progenitor cells raised the hope for successful treatment option against pulmonary fibrosis. Herein, we addressed the contribution of lung microenvironment and prominin-1(+) bone marrow-derived epithelial progenitor cells in the mouse model of bleomycin-induced experimental pulmonary fibrosis.Prominin-1(+) bone marrow-derived epithelial progenitors were expanded from adult mouse lungs and differentiated in vitro by cytokines and growth factors. Pulmonary fibrosis was induced in C57Bl/6 mice by intratracheal instillation of bleomycin. Prominin-1(+) progenitors were administered intratracheally at different time points after bleomycin challenge. Green fluorescence protein-expressing cells were used for cell tracking. Cell phenotypes were characterized by immunohistochemistry, flow cytometry and quantitative reverse transcription-polymerase chain reaction.Prominin-1(+) cells expanded from healthy lung represent common progenitors of alveolar type II epithelial cells, myofibroblasts, and macrophages. Administration of prominin-1(+) cells 2 hours after bleomycin instillation protects from pulmonary fibrosis, and some of progenitors differentiate into alveolar type II epithelial cells. In contrast, prominin-1(+) cells administered at day 7 or 14 lose their protective effects and differentiate into myofibroblasts and macrophages. Bleomycin challenge enhances accumulation of bone marrow-derived prominin-1(+) cells within inflamed lung. In contrast to prominin-1(+) cells from healthy lung, prominin-1(+) precursors isolated from inflamed organ lack regenerative properties but acquire myofibroblast and macrophage phenotypes.The microenvironment of inflamed lung impairs the regenerative capacity of bone marrow-derived prominin-1(+) progenitors and promotes their differentiation into pathogenic phenotypes.

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Importin 13 serves as a potential marker for corneal epithelial progenitor cells.

Publications

Importin 13 serves as a potential marker for corneal epithelial progenitor cells.

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