KIF5A transports collagen vesicles of myofibroblasts during pleural fibrosis
Abstract Fibrosis involves the production of extracellular matrix proteins in tissues and is often preceded by injury or trauma. In pleural fibrosis excess collagen deposition results in pleural thickening, increased stiffness and impaired lung function. Myofibroblasts are responsible for increased...
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Nature Portfolio
2017
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oai:doaj.org-article:9c07477bd0e4450b94bd1147a0932edd2021-12-02T15:05:35ZKIF5A transports collagen vesicles of myofibroblasts during pleural fibrosis10.1038/s41598-017-04437-72045-2322https://doaj.org/article/9c07477bd0e4450b94bd1147a0932edd2017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-04437-7https://doaj.org/toc/2045-2322Abstract Fibrosis involves the production of extracellular matrix proteins in tissues and is often preceded by injury or trauma. In pleural fibrosis excess collagen deposition results in pleural thickening, increased stiffness and impaired lung function. Myofibroblasts are responsible for increased collagen deposition, however the molecular mechanism of transportation of procollagen containing vesicles for secretion is unknown. Here, we studied the role of kinesin on collagen-1 (Col-1) containing vesicle transportation in human pleural mesothelial cells (HPMCs). Among a number of cargo transporting kinesins, KIF5A was notably upregulated during TGF-β induced mesothelial-mesenchymal transition (MesoMT). Using superresolution structured illumination microscopy and the DUO-Link technique, we found that KIF5A colocalized with Col-1 containing vesicles. KIF5A knock-down significantly reduced Col-1 secretion and attenuated TGF-β induced increment in Col-1 localization at cell peripheries. Live cell imaging revealed that GFP-KIF5A and mCherry-Col-1 containing vesicles moved together. Kymography showed that these molecules continuously move with a mean velocity of 0.56 μm/sec, suggesting that the movement is directional but not diffusion limited process. Moreover, KIF5A was notably upregulated along with Col-1 and α-smooth muscle actin in pleural thickening in the carbon-black bleomycin mouse model. These results support our hypothesis that KIF5A is responsible for collagen transportation and secretion from HPMCs.Hirotoshi KamataYoshikazu TsukasakiTsuyoshi SakaiReiko IkebeJulia WangAnn JeffersJake BorenShuzi OwensTakahiro SuzukiMasaaki HigashiharaSteven IdellTorry A. TuckerMitsuo IkebeNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017) |
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Medicine R Science Q |
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Medicine R Science Q Hirotoshi Kamata Yoshikazu Tsukasaki Tsuyoshi Sakai Reiko Ikebe Julia Wang Ann Jeffers Jake Boren Shuzi Owens Takahiro Suzuki Masaaki Higashihara Steven Idell Torry A. Tucker Mitsuo Ikebe KIF5A transports collagen vesicles of myofibroblasts during pleural fibrosis |
| description |
Abstract Fibrosis involves the production of extracellular matrix proteins in tissues and is often preceded by injury or trauma. In pleural fibrosis excess collagen deposition results in pleural thickening, increased stiffness and impaired lung function. Myofibroblasts are responsible for increased collagen deposition, however the molecular mechanism of transportation of procollagen containing vesicles for secretion is unknown. Here, we studied the role of kinesin on collagen-1 (Col-1) containing vesicle transportation in human pleural mesothelial cells (HPMCs). Among a number of cargo transporting kinesins, KIF5A was notably upregulated during TGF-β induced mesothelial-mesenchymal transition (MesoMT). Using superresolution structured illumination microscopy and the DUO-Link technique, we found that KIF5A colocalized with Col-1 containing vesicles. KIF5A knock-down significantly reduced Col-1 secretion and attenuated TGF-β induced increment in Col-1 localization at cell peripheries. Live cell imaging revealed that GFP-KIF5A and mCherry-Col-1 containing vesicles moved together. Kymography showed that these molecules continuously move with a mean velocity of 0.56 μm/sec, suggesting that the movement is directional but not diffusion limited process. Moreover, KIF5A was notably upregulated along with Col-1 and α-smooth muscle actin in pleural thickening in the carbon-black bleomycin mouse model. These results support our hypothesis that KIF5A is responsible for collagen transportation and secretion from HPMCs. |
| format |
article |
| author |
Hirotoshi Kamata Yoshikazu Tsukasaki Tsuyoshi Sakai Reiko Ikebe Julia Wang Ann Jeffers Jake Boren Shuzi Owens Takahiro Suzuki Masaaki Higashihara Steven Idell Torry A. Tucker Mitsuo Ikebe |
| author_facet |
Hirotoshi Kamata Yoshikazu Tsukasaki Tsuyoshi Sakai Reiko Ikebe Julia Wang Ann Jeffers Jake Boren Shuzi Owens Takahiro Suzuki Masaaki Higashihara Steven Idell Torry A. Tucker Mitsuo Ikebe |
| author_sort |
Hirotoshi Kamata |
| title |
KIF5A transports collagen vesicles of myofibroblasts during pleural fibrosis |
| title_short |
KIF5A transports collagen vesicles of myofibroblasts during pleural fibrosis |
| title_full |
KIF5A transports collagen vesicles of myofibroblasts during pleural fibrosis |
| title_fullStr |
KIF5A transports collagen vesicles of myofibroblasts during pleural fibrosis |
| title_full_unstemmed |
KIF5A transports collagen vesicles of myofibroblasts during pleural fibrosis |
| title_sort |
kif5a transports collagen vesicles of myofibroblasts during pleural fibrosis |
| publisher |
Nature Portfolio |
| publishDate |
2017 |
| url |
https://doaj.org/article/9c07477bd0e4450b94bd1147a0932edd |
| work_keys_str_mv |
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1718388783385149440 |