Antifibrotic Effect of Combined Treatment with Neuroleptic Drug and Immobilized Hyaluronidase in Pulmonary Fibrosis

Дыгай, А. М.; Скурихин, Е. Г.; Ермакова, Н. Н.; Першина, О. В.; Krupin, V. A.; Reztsova, A. M.; Ермолаева, Л. А.; Khmelevskaya, E. S.; Степанова, И. Э.; Artamonov, A. V.; Bekarev, A. A.; Мадонов, П. Г.; Kinsht, D. N.; Goldberg, V. Е.; Semiglazova, T. A.

doi:10.1007/s10517-013-1943-5

Cited by 8 publications

(3 citation statements)

References 9 publications

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“…Consistent with our previous study [27], no sample type preference was identified. HYAL1 was one of the top 25 genes that was significantly downregulated in IPF lung tissues, which supports the reported antifibrotic effect of hyaluronidases in lung fibrosis [34,36]. Our observation of reduced HYAL1 expression in IPF lung tissue was consistent with reports of the absence of HYAL1 mRNA in lung carcinoma cell lines [12] and reduced HYAL1 protein levels in endometrial carcinomas [13].…”

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confidence: 90%

HYAL1 Is Downregulated in Idiopathic Pulmonary Fibrosis and Inhibits HFL-1 Fibroblast Proliferation When Upregulated

Dong

Huang

et al. 2020

BioMed Research International

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Background. Idiopathic pulmonary fibrosis (IPF), the most common interstitial lung disease, arises from transforming growth factor beta 1- (TGFβ1-) induced aberrant fibroproliferation in response to epithelial injury. The TGFβ1 antagonists—hyaluronidases (HYALs)—have been used to clinically treat pulmonary fibrosis. This study focused on characterizing the effect of HYAL1, the main enzyme in hyaluronan degradation, on human lung fibroblast proliferation and apoptosis, and elucidating its potential underlying mechanism of action. Methods. We first performed microarray data mining of previously published gene expression datasets to identify key gene signatures in IPF lung tissues. HYAL1 expression levels in IPF and normal lung tissues were then characterized using immunohistochemistry followed by real-time quantitative reverse transcription-PCR (qRT-PCR) and western blot analysis on isolated fibroblasts from fresh lung tissues of IPF and healthy donors. A human fetal lung fibroblast HFL-1 cell line, which was used in place of primary lung fibroblasts, was used to assess the proliferative or apoptotic effects associated with lentiviral-induced HYAL1 overexpression using CCK-8 cell proliferation assay and Annexin V-APC staining. The identification of potentially associated molecular pathways was performed using microarray analysis followed by qRT-PCR and western blot analysis. Results. Lung tissue microarray data mining and immunohistochemistry revealed significantly downregulation of HYAL1 in IPF lung tissue. However, HYAL1 expression level in IPF fibroblasts was significantly upregulated at the mRNA level, but not altered at the protein level. HYAL1 overexpression in HFL-1 fibroblasts reduced fibroproliferation modestly but did not promote apoptosis. In addition, HYAL1 overexpression led to concomitant transcription factor downregulation, bone morphogenetic protein receptor 2 (BMPR2) signaling activation, but had no effect on TGFβ receptor 2 (TGFβR2) signaling. Conclusions. We showed that HYAL1 overexpression could prevent HFL-1 fibroproliferation. Furthermore, our findings suggest that transcriptional regulators and BMP receptor signaling may be involved in HYAL1 modulation in IPF therapy.

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confidence: 90%

HYAL1 Is Downregulated in Idiopathic Pulmonary Fibrosis and Inhibits HFL-1 Fibroblast Proliferation When Upregulated

Dong

Huang

et al. 2020

BioMed Research International

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“…Degradation of HA mostly results from the enzymatic action of HYAL [15] which was recognized as a “spreading factor” by hydrolyzing the dermal barrier. HYAL has been therapeutically used for many years based on their properties in facilitating the subcutaneous infusion and dispersion of fluids thus improving absorption of drugs [16] – [19] , besides its ability to reduce bleomycin-induced lung injury and fibrosis [20] – [22] .…”

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confidence: 99%

Hyaluronidase Modulates Inflammatory Response and Accelerates the Cutaneous Wound Healing

et al. 2014

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Hyaluronidases are enzymes that degrade hyaluronan an important constituent of the extracellular matrix. They have been used as a spreading agent, improving the absorption of drugs and facilitating the subcutaneous infusion of fluids. Here, we investigated the influence of bovine testes hyaluronidase (HYAL) during cutaneous wound healing in in vitro and in vivo assays. We demonstrated in the wound scratch assay that HYAL increased the migration and proliferation of fibroblasts in vitro at low concentration, e.g. 0.1 U HYAL enhanced the cell number by 20%. HYAL presented faster and higher reepithelialization in in vivo full-thickness excisional wounds generated on adult Wistar rats back skin already in the early phase at 2nd day post operatory compared to vehicle-control group. Wound closured area observed in the 16 U and 32 U HYAL treated rats reached 38% and 46% compared to 19% in the controls, respectively. Histological and biochemical analyses supported the clinical observations and showed that HYAL treated wounds exhibited increased granulation tissue, diminished edema formation and regulated the inflammatory response by modulating the release of pro and anti-inflammatory cytokines, growth factor and eicosanoids mediators. Moreover, HYAL increased gene expression of peroxisome proliferator-activated receptors (PPAR) γ and PPAR β/δ, the collagen content in the early stages of healing processes as well as angiogenesis. Altogether these data revealed that HYAL accelerates wound healing processes and might be beneficial for treating wound disorders.

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“…Antifi brotic activity of imHD was previously demonstrated on the model of a lung injury infl icted by a single bleomycin dose (partially reversible pneumofi brosis) [1].…”

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confidence: 98%

Antifibrotic Effects of Immobilized Hyaluronidase in Repeated Bleomycin-Induced Lesions of the Alveolar Epithelium

Дыгай¹,

Скурихин²,

Ермакова³

et al. 2013

Bull Exp Biol Med

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Antifibrotic activity of testicular hyaluronidase, immobilized on polyethylenoxide and obtained by electron beam synthesis, was studied on the model of bleomycin injuries to the alveolar epithelium (irreversible pneumofibrosis) in C57Bl/6 mice and compared to the effect of testicular hyaluronidase. Intranasal therapy with immobilized and testicular hyaluronidases prevented the deposition of fibrotic mass in the parenchyma of "bleomycin" lungs. The effect of immobilized hyaluronidase was more pronounced than that of testicular hyaluronidase. The studied compounds were virtually inessential for infiltration of the alveolar interstitium and alveolar tracts by lymphocytes, macrophages, neutrophils, and plasma cells. Unchanged histoarchitectonics of bleomycin-damaged lungs in immobilized hyaluronidase therapy was due to suppression of the progenitor fibroblast cells (CD45(-)).

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Antifibrotic Effect of Combined Treatment with Neuroleptic Drug and Immobilized Hyaluronidase in Pulmonary Fibrosis

Cited by 8 publications

References 9 publications

HYAL1 Is Downregulated in Idiopathic Pulmonary Fibrosis and Inhibits HFL-1 Fibroblast Proliferation When Upregulated

HYAL1 Is Downregulated in Idiopathic Pulmonary Fibrosis and Inhibits HFL-1 Fibroblast Proliferation When Upregulated

Hyaluronidase Modulates Inflammatory Response and Accelerates the Cutaneous Wound Healing

Antifibrotic Effects of Immobilized Hyaluronidase in Repeated Bleomycin-Induced Lesions of the Alveolar Epithelium

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