OBJECTIVE: Defective apoptosis contributes to the massive synovial hyperplasia in rheumatoid arthritis (RA), but the mechanism is largely unknown. To investigate the reasons for the reduced apoptosis in RA synovium, we analyzed autophagy and its relationship to apoptosis in synovial tissues from RA and osteoarthritis (OA) patients. METHODS: Synovial tissues were obtained from seven RA and 12 OA patients undergoing knee replacement surgery. Apoptosis was detected by the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay and staining for p85 fragment of PolyADP-ribose polymerase (PARP). Autophagy was determined by immunoblotting for the autophagic markers Beclin-1 and LC3. MicroRNA-30a (miR-30a), which targets Beclin-1, was measured by real-time RT-PCR. The interplay between autophagy and apoptosis was determined via Spearman's correlation analysis. RESULTS: In comparison with OA, the synovial tissues from RA displayed decreased TUNEL-positive nuclei (P < 0.01). In contrast, Beclin-1 and LC3 were overexpressed in the synovial lining layers of RA, which was correlated with decreased levels of miR-30a. Moreover, there was a significant reverse relationship between apoptosis and autophagy in RA synovial tissues (P < 0.01 and r = -0.8937). CONCLUSION: The impaired apoptosis in RA synovium might result from increased autophagy, which in turn could be due to the deregulation of miRNA-30a.
OBJECTIVE: Defective apoptosis contributes to the massive synovial hyperplasia in rheumatoid arthritis (RA), but the mechanism is largely unknown. To investigate the reasons for the reduced apoptosis in RA synovium, we analyzed autophagy and its relationship to apoptosis in synovial tissues from RA and osteoarthritis (OA) patients. METHODS: Synovial tissues were obtained from seven RA and 12 OA patients undergoing knee replacement surgery. Apoptosis was detected by the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay and staining for p85 fragment of PolyADP-ribose polymerase (PARP). Autophagy was determined by immunoblotting for the autophagic markers Beclin-1 and LC3. MicroRNA-30a (miR-30a), which targets Beclin-1, was measured by real-time RT-PCR. The interplay between autophagy and apoptosis was determined via Spearman's correlation analysis. RESULTS: In comparison with OA, the synovial tissues from RA displayed decreased TUNEL-positive nuclei (P < 0.01). In contrast, Beclin-1 and LC3 were overexpressed in the synovial lining layers of RA, which was correlated with decreased levels of miR-30a. Moreover, there was a significant reverse relationship between apoptosis and autophagy in RA synovial tissues (P < 0.01 and r = -0.8937). CONCLUSION: The impaired apoptosis in RA synovium might result from increased autophagy, which in turn could be due to the deregulation of miRNA-30a.
Authors: Shaochun Bai; Hongtao Liu; Kun-Hung Chen; Polikseni Eksarko; Harris Perlman; Terry L Moore; Richard M Pope Journal: Arthritis Rheum Date: 2004-12
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Authors: Weijie Zhan; Tao Yan; Jiawen Gao; Minkai Song; Ting Wang; Fei Lin; Haiyu Zhou; Li Li; Chao Zhang Journal: Nan Fang Yi Ke Da Xue Xue Bao Date: 2022-02-20
Authors: Daniel J Klionsky; Giulia Petroni; Ravi K Amaravadi; Eric H Baehrecke; Andrea Ballabio; Patricia Boya; José Manuel Bravo-San Pedro; Ken Cadwell; Francesco Cecconi; Augustine M K Choi; Mary E Choi; Charleen T Chu; Patrice Codogno; Maria Isabel Colombo; Ana Maria Cuervo; Vojo Deretic; Ivan Dikic; Zvulun Elazar; Eeva-Liisa Eskelinen; Gian Maria Fimia; David A Gewirtz; Douglas R Green; Malene Hansen; Marja Jäättelä; Terje Johansen; Gábor Juhász; Vassiliki Karantza; Claudine Kraft; Guido Kroemer; Nicholas T Ktistakis; Sharad Kumar; Carlos Lopez-Otin; Kay F Macleod; Frank Madeo; Jennifer Martinez; Alicia Meléndez; Noboru Mizushima; Christian Münz; Josef M Penninger; Rushika M Perera; Mauro Piacentini; Fulvio Reggiori; David C Rubinsztein; Kevin M Ryan; Junichi Sadoshima; Laura Santambrogio; Luca Scorrano; Hans-Uwe Simon; Anna Katharina Simon; Anne Simonsen; Alexandra Stolz; Nektarios Tavernarakis; Sharon A Tooze; Tamotsu Yoshimori; Junying Yuan; Zhenyu Yue; Qing Zhong; Lorenzo Galluzzi; Federico Pietrocola Journal: EMBO J Date: 2021-08-30 Impact factor: 14.012