Modulation of bleomycin-induced lung fibrosis by pegylated hyaluronidase and dopamine receptor antagonist in mice.

Hyaluronidases are groups of enzymes that degrade hyaluronic acid (HA). To stop enzymatic hydrolysis we modified testicular hyaluronidase (HYAL) by activated polyethylene oxide with the help of electron-beam synthesis. As a result we received pegylated hyaluronidase (pegHYAL). Spiperone is a selecti...

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Main Authors: Evgenii Germanovich Skurikhin, Olga Victorovna Pershina, Alena Mikhaylovna Reztsova, Natalia Nikolaevna Ermakova, Ekaterina Sergeevna Khmelevskaya, Vycheslav Andreevich Krupin, Inna Ernestovna Stepanova, Andrew Vladimirovich Artamonov, Andrew Alexandrovich Bekarev, Pavel Gennadjevich Madonov, Alexander Mikhaylovich Dygai
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2015-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC4415936?pdf=render
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spelling doaj-2de52e867ebe46538cc1bffb693cb2ea2020-11-25T01:33:20ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01104e012506510.1371/journal.pone.0125065Modulation of bleomycin-induced lung fibrosis by pegylated hyaluronidase and dopamine receptor antagonist in mice.Evgenii Germanovich SkurikhinOlga Victorovna PershinaAlena Mikhaylovna ReztsovaNatalia Nikolaevna ErmakovaEkaterina Sergeevna KhmelevskayaVycheslav Andreevich KrupinInna Ernestovna StepanovaAndrew Vladimirovich ArtamonovAndrew Alexandrovich BekarevPavel Gennadjevich MadonovAlexander Mikhaylovich DygaiHyaluronidases are groups of enzymes that degrade hyaluronic acid (HA). To stop enzymatic hydrolysis we modified testicular hyaluronidase (HYAL) by activated polyethylene oxide with the help of electron-beam synthesis. As a result we received pegylated hyaluronidase (pegHYAL). Spiperone is a selective D2 dopamine receptor antagonist. It was demonstrated on the model of a single bleomycin damage of alveolar epithelium that during the inflammatory phase monotherapy by pegHYAL or spiperone reduced the populations of hematopoietic stem /progenitor cells in the lung parenchyma. PegHYAL also reduced the levels of transforming growth factor (TGF)-β, interleukin (IL)-1β, tumor necrosis factor (TNF)-α in the serum and lungs, while spiperone reduced the level of the serum IL-1β. Polytherapy by spiperone and pegHYAL caused the increase of the quantity of hematopoietic stem/ progenitor cells in the lungs. Such an influx of blood cell precursors was observed on the background of considerable fall level of TGF-β and the increase level of TNF-α in the serum and lungs. These results show pegHYAL reduced the bleomycin-induced fibrosis reaction (production and accumulation of collagen) in the lung parenchyma. This effect was observed at a single and repetitive bleomycin damage of alveolar epithelium, the antifibrotic activity of pegHYAL surpassing the activity of testicular HYAL. The antifibrotic effect of pegHYAL is enhanced by an additional instillation of spiperone. Therapy by pegHYAL causes the flow of CD31‒ CD34‒ CD45‒ CD44+ CD73+ CD90+ CD106+-cells into the fibrous lungs. These cells are incapable of differentiating into fibroblast cells. Spiperone instillation separately or together with pegHYAL reduced the MSC-like cells considerably. These data enable us to assume, that pegHYAL is a new and promising instrument both for preventive and therapy of toxic pneumofibrosis. The blockage of D2 dopamine receptors with the following change of hyaluronan matrix can be considered as a new strategy in treatment of pneumofibrosis.http://europepmc.org/articles/PMC4415936?pdf=render
collection DOAJ
language English
format Article
sources DOAJ
author Evgenii Germanovich Skurikhin
Olga Victorovna Pershina
Alena Mikhaylovna Reztsova
Natalia Nikolaevna Ermakova
Ekaterina Sergeevna Khmelevskaya
Vycheslav Andreevich Krupin
Inna Ernestovna Stepanova
Andrew Vladimirovich Artamonov
Andrew Alexandrovich Bekarev
Pavel Gennadjevich Madonov
Alexander Mikhaylovich Dygai
spellingShingle Evgenii Germanovich Skurikhin
Olga Victorovna Pershina
Alena Mikhaylovna Reztsova
Natalia Nikolaevna Ermakova
Ekaterina Sergeevna Khmelevskaya
Vycheslav Andreevich Krupin
Inna Ernestovna Stepanova
Andrew Vladimirovich Artamonov
Andrew Alexandrovich Bekarev
Pavel Gennadjevich Madonov
Alexander Mikhaylovich Dygai
Modulation of bleomycin-induced lung fibrosis by pegylated hyaluronidase and dopamine receptor antagonist in mice.
PLoS ONE
author_facet Evgenii Germanovich Skurikhin
Olga Victorovna Pershina
Alena Mikhaylovna Reztsova
Natalia Nikolaevna Ermakova
Ekaterina Sergeevna Khmelevskaya
Vycheslav Andreevich Krupin
Inna Ernestovna Stepanova
Andrew Vladimirovich Artamonov
Andrew Alexandrovich Bekarev
Pavel Gennadjevich Madonov
Alexander Mikhaylovich Dygai
author_sort Evgenii Germanovich Skurikhin
title Modulation of bleomycin-induced lung fibrosis by pegylated hyaluronidase and dopamine receptor antagonist in mice.
title_short Modulation of bleomycin-induced lung fibrosis by pegylated hyaluronidase and dopamine receptor antagonist in mice.
title_full Modulation of bleomycin-induced lung fibrosis by pegylated hyaluronidase and dopamine receptor antagonist in mice.
title_fullStr Modulation of bleomycin-induced lung fibrosis by pegylated hyaluronidase and dopamine receptor antagonist in mice.
title_full_unstemmed Modulation of bleomycin-induced lung fibrosis by pegylated hyaluronidase and dopamine receptor antagonist in mice.
title_sort modulation of bleomycin-induced lung fibrosis by pegylated hyaluronidase and dopamine receptor antagonist in mice.
publisher Public Library of Science (PLoS)
series PLoS ONE
issn 1932-6203
publishDate 2015-01-01
description Hyaluronidases are groups of enzymes that degrade hyaluronic acid (HA). To stop enzymatic hydrolysis we modified testicular hyaluronidase (HYAL) by activated polyethylene oxide with the help of electron-beam synthesis. As a result we received pegylated hyaluronidase (pegHYAL). Spiperone is a selective D2 dopamine receptor antagonist. It was demonstrated on the model of a single bleomycin damage of alveolar epithelium that during the inflammatory phase monotherapy by pegHYAL or spiperone reduced the populations of hematopoietic stem /progenitor cells in the lung parenchyma. PegHYAL also reduced the levels of transforming growth factor (TGF)-β, interleukin (IL)-1β, tumor necrosis factor (TNF)-α in the serum and lungs, while spiperone reduced the level of the serum IL-1β. Polytherapy by spiperone and pegHYAL caused the increase of the quantity of hematopoietic stem/ progenitor cells in the lungs. Such an influx of blood cell precursors was observed on the background of considerable fall level of TGF-β and the increase level of TNF-α in the serum and lungs. These results show pegHYAL reduced the bleomycin-induced fibrosis reaction (production and accumulation of collagen) in the lung parenchyma. This effect was observed at a single and repetitive bleomycin damage of alveolar epithelium, the antifibrotic activity of pegHYAL surpassing the activity of testicular HYAL. The antifibrotic effect of pegHYAL is enhanced by an additional instillation of spiperone. Therapy by pegHYAL causes the flow of CD31‒ CD34‒ CD45‒ CD44+ CD73+ CD90+ CD106+-cells into the fibrous lungs. These cells are incapable of differentiating into fibroblast cells. Spiperone instillation separately or together with pegHYAL reduced the MSC-like cells considerably. These data enable us to assume, that pegHYAL is a new and promising instrument both for preventive and therapy of toxic pneumofibrosis. The blockage of D2 dopamine receptors with the following change of hyaluronan matrix can be considered as a new strategy in treatment of pneumofibrosis.
url http://europepmc.org/articles/PMC4415936?pdf=render
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