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Mechanisms of Endothelial-to-Mesenchymal Transition Induction by Extracellular Matrix Components in Pulmonary Fibrosis

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Bulletin of Experimental Biology and Medicine Aims and scope

Idiopathic pulmonary fibrosis can be caused by different factors, including accumulation of pathological extracellular matrix (ECM) with abnormal composition, stiffness, and architecture in the lung tissue. We studied the effect of ECM produced by lung fibroblasts of healthy mice or mice with bleomycin-induced pulmonary fibrosis on the process of endothelialto- mesenchymal transition, one of the main sources of effector myofibroblasts in fibrosis progression. Despite stimulation of spontaneous and TGFβ-1-induced differentiation of fibroblasts into myofibroblasts by fibrotic ECM, the appearance of α-SMA, the main marker of myofibroblasts, and its integration in stress fibrils in endotheliocytes were not observed under similar conditions. However, the expression of transcription factors SNAI1 and SNAI2/Slug and the production of components of fibrotic ECM (specific EDA-fibronectin splice form and collagen type I) were increased in endotheliocytes cultured on fibrotic ECM. Endothelium also demonstrated increased cell velocity in the models of directed cell migration. These data indicate activation of the intermediate state of the endothelial-to-mesenchymal transition in endotheliocytes upon contact with fibrotic, but not normal stromal matrix. In combination with the complex microenvironment that develops during fibrosis progression, it can lead to the replenishment of myofibroblasts pool from the resident endothelium.

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Authors and Affiliations

  1. Institute for Regenerative Medicine, Medical Research and Educational Centre, M. V. Lomonosov Moscow State University, Moscow, Russia

    O. A. Grigorieva, M. A. Vigovskiy, U. D. Dyachkova, N. A. Basalova, N. A. Aleksandrushkina, M. A. Kulebyakina, I. L. Zaitsev, V. S. Popov & A. Yu. Efimenko

Authors
  1. O. A. Grigorieva
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  2. M. A. Vigovskiy
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  3. U. D. Dyachkova
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  4. N. A. Basalova
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  5. N. A. Aleksandrushkina
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  6. M. A. Kulebyakina
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  7. I. L. Zaitsev
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  8. V. S. Popov
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  9. A. Yu. Efimenko
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Corresponding author

Correspondence to O. A. Grigorieva.

Additional information

Translated from Kletochnye Tekhnologii v Biologii i Meditsine, No. 2, pp. 97-106, June, 2021

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Grigorieva, O.A., Vigovskiy, M.A., Dyachkova, U.D. et al. Mechanisms of Endothelial-to-Mesenchymal Transition Induction by Extracellular Matrix Components in Pulmonary Fibrosis. Bull Exp Biol Med 171, 523–531 (2021). https://doi.org/10.1007/s10517-021-05264-7

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  • DOI: https://doi.org/10.1007/s10517-021-05264-7

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