Neutrophil elastase in the development of nephrogenic systemic fibrosis (NSF)-like skin lesion in renal failure mouse model.

Although neutrophil elastase (NE) may play a role in lung fibrosis and liver fibrosis, NE involvement in the development of nephrogenic systemic fibrosis has been unclear. We investigated the involvement of NE in the development of nephrogenic systemic fibrosis-like skin lesions post-injections of l...

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Autores principales: A Adhipatria P Kartamihardja, Syahla Nisaa Amalia, Akiko Sekiguchi, Anu Bhattarai, Ayako Taketomi-Takahashi, Sei-Ichiro Motegi, Hiroshi Koyama, Yoshito Tsushima
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Publicado: Public Library of Science (PLoS) 2021
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spelling oai:doaj.org-article:1c855d702d4b45e1ba29edf36861218a2021-12-02T20:19:10ZNeutrophil elastase in the development of nephrogenic systemic fibrosis (NSF)-like skin lesion in renal failure mouse model.1932-620310.1371/journal.pone.0259211https://doaj.org/article/1c855d702d4b45e1ba29edf36861218a2021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0259211https://doaj.org/toc/1932-6203Although neutrophil elastase (NE) may play a role in lung fibrosis and liver fibrosis, NE involvement in the development of nephrogenic systemic fibrosis has been unclear. We investigated the involvement of NE in the development of nephrogenic systemic fibrosis-like skin lesions post-injections of linear gadolinium-based contrast agents in renal failure mouse models. Renal failure mouse models were randomly divided into three groups: control group (saline), gadodiamide group, and gadopentetate group. Each solution was intravenously administered three times per week for three weeks. The mice were observed daily for skin lesions. Quantification of skin lesions, infiltrating inflammatory cells, and profibrotic cytokines in the affected skin was performed by immunostaining and reverse-transcription polymerase chain reaction (RT-PCR). Blood samples were collected from the facial vein to quantify NE enzymatic activity. The 158Gd concentrations in each sample were quantified using inductively coupled plasma mass spectrometry (ICP-MS). In the gadodiamide group, the mRNA expression of fibrotic markers was increased in the skin lesions compared to the control group. In the gadopentetate group, only collagen 1α and TGF-β mRNA expression were higher than in the control group. The expression of CD3+, CD68+, NE cells and the NE activity in the blood serum were significantly higher in the gadodiamide and gadopentetate groups compared to the control group. Gadolinium concentration in the skin of the gadodiamide group was significantly higher than the gadopentetate group, while almost no traces of gadolinium were found in the control group. Although gadopentetate and gadodiamide affected the fibrotic markers in the skin differently, NE may be involved in the development of fibrosis linked to the GBCAs injections in renal failure mouse models.A Adhipatria P KartamihardjaSyahla Nisaa AmaliaAkiko SekiguchiAnu BhattaraiAyako Taketomi-TakahashiSei-Ichiro MotegiHiroshi KoyamaYoshito TsushimaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 10, p e0259211 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
A Adhipatria P Kartamihardja
Syahla Nisaa Amalia
Akiko Sekiguchi
Anu Bhattarai
Ayako Taketomi-Takahashi
Sei-Ichiro Motegi
Hiroshi Koyama
Yoshito Tsushima
Neutrophil elastase in the development of nephrogenic systemic fibrosis (NSF)-like skin lesion in renal failure mouse model.
description Although neutrophil elastase (NE) may play a role in lung fibrosis and liver fibrosis, NE involvement in the development of nephrogenic systemic fibrosis has been unclear. We investigated the involvement of NE in the development of nephrogenic systemic fibrosis-like skin lesions post-injections of linear gadolinium-based contrast agents in renal failure mouse models. Renal failure mouse models were randomly divided into three groups: control group (saline), gadodiamide group, and gadopentetate group. Each solution was intravenously administered three times per week for three weeks. The mice were observed daily for skin lesions. Quantification of skin lesions, infiltrating inflammatory cells, and profibrotic cytokines in the affected skin was performed by immunostaining and reverse-transcription polymerase chain reaction (RT-PCR). Blood samples were collected from the facial vein to quantify NE enzymatic activity. The 158Gd concentrations in each sample were quantified using inductively coupled plasma mass spectrometry (ICP-MS). In the gadodiamide group, the mRNA expression of fibrotic markers was increased in the skin lesions compared to the control group. In the gadopentetate group, only collagen 1α and TGF-β mRNA expression were higher than in the control group. The expression of CD3+, CD68+, NE cells and the NE activity in the blood serum were significantly higher in the gadodiamide and gadopentetate groups compared to the control group. Gadolinium concentration in the skin of the gadodiamide group was significantly higher than the gadopentetate group, while almost no traces of gadolinium were found in the control group. Although gadopentetate and gadodiamide affected the fibrotic markers in the skin differently, NE may be involved in the development of fibrosis linked to the GBCAs injections in renal failure mouse models.
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author A Adhipatria P Kartamihardja
Syahla Nisaa Amalia
Akiko Sekiguchi
Anu Bhattarai
Ayako Taketomi-Takahashi
Sei-Ichiro Motegi
Hiroshi Koyama
Yoshito Tsushima
author_facet A Adhipatria P Kartamihardja
Syahla Nisaa Amalia
Akiko Sekiguchi
Anu Bhattarai
Ayako Taketomi-Takahashi
Sei-Ichiro Motegi
Hiroshi Koyama
Yoshito Tsushima
author_sort A Adhipatria P Kartamihardja
title Neutrophil elastase in the development of nephrogenic systemic fibrosis (NSF)-like skin lesion in renal failure mouse model.
title_short Neutrophil elastase in the development of nephrogenic systemic fibrosis (NSF)-like skin lesion in renal failure mouse model.
title_full Neutrophil elastase in the development of nephrogenic systemic fibrosis (NSF)-like skin lesion in renal failure mouse model.
title_fullStr Neutrophil elastase in the development of nephrogenic systemic fibrosis (NSF)-like skin lesion in renal failure mouse model.
title_full_unstemmed Neutrophil elastase in the development of nephrogenic systemic fibrosis (NSF)-like skin lesion in renal failure mouse model.
title_sort neutrophil elastase in the development of nephrogenic systemic fibrosis (nsf)-like skin lesion in renal failure mouse model.
publisher Public Library of Science (PLoS)
publishDate 2021
url https://doaj.org/article/1c855d702d4b45e1ba29edf36861218a
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