Cargando…

Hypoxia-induced autophagy is inhibited by PADI4 knockdown, which promotes apoptosis of fibroblast-like synoviocytes in rheumatoid arthritis

Impaired apoptosis of rheumatoid arthritis (RA)-fibroblast-like synoviocytes (FLS) is pivotal in the process of RA. Peptidyl arginine deiminase type IV (PADI4) is associated with autoantibody regulation via histone citrullination in RA. The present study aimed to investigate the role of PADI4 in the...

Descripción completa

Detalles Bibliográficos
Autores principales: Fan, Tingting, Zhang, Changsong, Zong, Ming, Fan, Lieying
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5865976/
https://www.ncbi.nlm.nih.gov/pubmed/29393388
http://dx.doi.org/10.3892/mmr.2018.8501
_version_ 1783308785235787776
author Fan, Tingting
Zhang, Changsong
Zong, Ming
Fan, Lieying
author_facet Fan, Tingting
Zhang, Changsong
Zong, Ming
Fan, Lieying
author_sort Fan, Tingting
collection PubMed
description Impaired apoptosis of rheumatoid arthritis (RA)-fibroblast-like synoviocytes (FLS) is pivotal in the process of RA. Peptidyl arginine deiminase type IV (PADI4) is associated with autoantibody regulation via histone citrullination in RA. The present study aimed to investigate the role of PADI4 in the apoptosis of RA-FLS. FLS were isolated from patients with RA and a rat model. The effects of PADI4 on RA-FLS were investigated in vitro and in vivo. Hypoxia-induced autophagy was induced by 1% O(2) and was detected by immunohistochemical and immunofluorescence analysis; in addition, apoptosis was detected by flow cytometry. RA-FLS obtained from RA rat model exhibited significant proliferation under severe hypoxia conditions. Hypoxia also significantly induced autophagy and elevated the expression of PADI4. Subsequently, short hairpin RNA-mediated PADI4 knockdown was demonstrated to significantly inhibit hypoxia-induced autophagy and promote apoptosis in RA-FLS. The results of these in vitro and in vivo studies suggested that PADI4 may be closely associated with hypoxia-induced autophagy, and the inhibition of hypoxia-induced autophagy by PADI4 knockdown may contribute to an increase in the apoptosis of RA-FLS.
format Online
Article
Text
id pubmed-5865976
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher D.A. Spandidos
record_format MEDLINE/PubMed
spelling pubmed-58659762018-03-28 Hypoxia-induced autophagy is inhibited by PADI4 knockdown, which promotes apoptosis of fibroblast-like synoviocytes in rheumatoid arthritis Fan, Tingting Zhang, Changsong Zong, Ming Fan, Lieying Mol Med Rep Articles Impaired apoptosis of rheumatoid arthritis (RA)-fibroblast-like synoviocytes (FLS) is pivotal in the process of RA. Peptidyl arginine deiminase type IV (PADI4) is associated with autoantibody regulation via histone citrullination in RA. The present study aimed to investigate the role of PADI4 in the apoptosis of RA-FLS. FLS were isolated from patients with RA and a rat model. The effects of PADI4 on RA-FLS were investigated in vitro and in vivo. Hypoxia-induced autophagy was induced by 1% O(2) and was detected by immunohistochemical and immunofluorescence analysis; in addition, apoptosis was detected by flow cytometry. RA-FLS obtained from RA rat model exhibited significant proliferation under severe hypoxia conditions. Hypoxia also significantly induced autophagy and elevated the expression of PADI4. Subsequently, short hairpin RNA-mediated PADI4 knockdown was demonstrated to significantly inhibit hypoxia-induced autophagy and promote apoptosis in RA-FLS. The results of these in vitro and in vivo studies suggested that PADI4 may be closely associated with hypoxia-induced autophagy, and the inhibition of hypoxia-induced autophagy by PADI4 knockdown may contribute to an increase in the apoptosis of RA-FLS. D.A. Spandidos 2018-04 2018-01-26 /pmc/articles/PMC5865976/ /pubmed/29393388 http://dx.doi.org/10.3892/mmr.2018.8501 Text en Copyright: © Fan et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Fan, Tingting
Zhang, Changsong
Zong, Ming
Fan, Lieying
Hypoxia-induced autophagy is inhibited by PADI4 knockdown, which promotes apoptosis of fibroblast-like synoviocytes in rheumatoid arthritis
title Hypoxia-induced autophagy is inhibited by PADI4 knockdown, which promotes apoptosis of fibroblast-like synoviocytes in rheumatoid arthritis
title_full Hypoxia-induced autophagy is inhibited by PADI4 knockdown, which promotes apoptosis of fibroblast-like synoviocytes in rheumatoid arthritis
title_fullStr Hypoxia-induced autophagy is inhibited by PADI4 knockdown, which promotes apoptosis of fibroblast-like synoviocytes in rheumatoid arthritis
title_full_unstemmed Hypoxia-induced autophagy is inhibited by PADI4 knockdown, which promotes apoptosis of fibroblast-like synoviocytes in rheumatoid arthritis
title_short Hypoxia-induced autophagy is inhibited by PADI4 knockdown, which promotes apoptosis of fibroblast-like synoviocytes in rheumatoid arthritis
title_sort hypoxia-induced autophagy is inhibited by padi4 knockdown, which promotes apoptosis of fibroblast-like synoviocytes in rheumatoid arthritis
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5865976/
https://www.ncbi.nlm.nih.gov/pubmed/29393388
http://dx.doi.org/10.3892/mmr.2018.8501
work_keys_str_mv AT fantingting hypoxiainducedautophagyisinhibitedbypadi4knockdownwhichpromotesapoptosisoffibroblastlikesynoviocytesinrheumatoidarthritis
AT zhangchangsong hypoxiainducedautophagyisinhibitedbypadi4knockdownwhichpromotesapoptosisoffibroblastlikesynoviocytesinrheumatoidarthritis
AT zongming hypoxiainducedautophagyisinhibitedbypadi4knockdownwhichpromotesapoptosisoffibroblastlikesynoviocytesinrheumatoidarthritis
AT fanlieying hypoxiainducedautophagyisinhibitedbypadi4knockdownwhichpromotesapoptosisoffibroblastlikesynoviocytesinrheumatoidarthritis