Dec2 attenuates autophagy in inflamed periodontal tissues
Abstract Introduction Transcriptional regulation of autophagy depends on the transcription factors coordinated inflammatory feedback mechanism. Here, we provide a comprehensive functional characterization of periodontal ligament fibroblasts (PDLFs) treated with Porphyromonas gingivalis lipopolysacch...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2021-03-01
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| Series: | Immunity, Inflammation and Disease |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/iid3.389 |
| _version_ | 1819119796347731968 |
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| author | Shunichi Oka Xiaoyan Li Fuyuki Sato Fengzhu Zhang Nitesh Tewari Chongchong Chen Liangjun Zhong Makoto Makishima Yi Liu Ujjal K. Bhawal |
| author_facet | Shunichi Oka Xiaoyan Li Fuyuki Sato Fengzhu Zhang Nitesh Tewari Chongchong Chen Liangjun Zhong Makoto Makishima Yi Liu Ujjal K. Bhawal |
| author_sort | Shunichi Oka |
| collection | DOAJ |
| description | Abstract Introduction Transcriptional regulation of autophagy depends on the transcription factors coordinated inflammatory feedback mechanism. Here, we provide a comprehensive functional characterization of periodontal ligament fibroblasts (PDLFs) treated with Porphyromonas gingivalis lipopolysaccharide (LPS), aiming to reveal previously unappreciated biological changes and to investigate how a transcription factor differentiated embryonic chondrocytes 2 (Dec2)‐deficient environment influences the function of autophagy in nflamed human PDLFs. Methods A Dec2‐deficient (Dec2KO) experimental periodontal inflammation mouse model and treatment with P. gingivalis LPS were employed to examine the role of autophagy in PDLFs using hematoxylin and eosin staining and immunohistochemistry in vivo. A Dec2 small interfering RNA (siRNA) was used to modulate autophagy, and the effect of autophagy on the Dec2 pathway was explored using real‐time polymerase chain reaction and western blot analysis in vitro. Results LPS‐treated human PDLFs (HPDLFs) induced autophagy, as demonstrated by the enhanced levels of microtubule‐associated protein 1 light chain 3‐II (LC3‐II) and the induction of ATG5, Beclin1, and Dec2. Compared with a scrambled siRNA, a Dec2 siRNA triggered the detrimental influences of LPS and markedly enhanced autophagy expression in inflamed HPDLFs. The expression of phosphorylated ERK was increased and levels of phosphorylated mammalian target of rapamycin (mTOR) were decreased after exposure to LPS in Dec2 siRNA transfected HPDLFs. The Dec2KO model exhibited that P. gingivalis in Dec2 deficient conditions increases the inflammation of PDLFs by regulating autophagy. Conclusions These results demonstrate that a Dec2 deficiency can alleviate LPS‐induced inflammation via the ERK/mTOR signaling pathway by regulating autophagy, conceivably delivering a novel approach for the detection of periodontal treatments. |
| first_indexed | 2024-12-22T06:10:28Z |
| format | Article |
| id | doaj.art-c095984069c340a0925e87fe8f48824b |
| institution | Directory Open Access Journal |
| issn | 2050-4527 |
| language | English |
| last_indexed | 2024-12-22T06:10:28Z |
| publishDate | 2021-03-01 |
| publisher | Wiley |
| record_format | Article |
| series | Immunity, Inflammation and Disease |
| spelling | doaj.art-c095984069c340a0925e87fe8f48824b2022-12-21T18:36:16ZengWileyImmunity, Inflammation and Disease2050-45272021-03-019126527310.1002/iid3.389Dec2 attenuates autophagy in inflamed periodontal tissuesShunichi Oka0Xiaoyan Li1Fuyuki Sato2Fengzhu Zhang3Nitesh Tewari4Chongchong Chen5Liangjun Zhong6Makoto Makishima7Yi Liu8Ujjal K. Bhawal9Department of Anesthesiology Nihon University School of Dentistry Tokyo JapanLaboratory of Tissue Regeneration and Immunology and Department of Periodontics, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction Capital Medical University School of Stomatology Beijing People's Republic of ChinaPathology Division Shizuoka Cancer Center Shizuoka JapanDepartment of Anesthesiology Nihon University School of Dentistry at Matsudo Chiba JapanDivision of Pedodontics and Preventive Dentistry, Centre for Dental Education and Research All India Institute of Medical Sciences New Delhi IndiaDepartment of Stomatology Hangzhou Normal University Hangzhou People's Republic of ChinaDepartment of Stomatology Hangzhou Normal University Hangzhou People's Republic of ChinaDivision of Biochemistry, Department of Biomedical Sciences Nihon University School of Medicine Tokyo JapanLaboratory of Tissue Regeneration and Immunology and Department of Periodontics, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction Capital Medical University School of Stomatology Beijing People's Republic of ChinaDepartment of Disaster Medicine and Dental Sociology Kanagawa Dental University Yokosuka JapanAbstract Introduction Transcriptional regulation of autophagy depends on the transcription factors coordinated inflammatory feedback mechanism. Here, we provide a comprehensive functional characterization of periodontal ligament fibroblasts (PDLFs) treated with Porphyromonas gingivalis lipopolysaccharide (LPS), aiming to reveal previously unappreciated biological changes and to investigate how a transcription factor differentiated embryonic chondrocytes 2 (Dec2)‐deficient environment influences the function of autophagy in nflamed human PDLFs. Methods A Dec2‐deficient (Dec2KO) experimental periodontal inflammation mouse model and treatment with P. gingivalis LPS were employed to examine the role of autophagy in PDLFs using hematoxylin and eosin staining and immunohistochemistry in vivo. A Dec2 small interfering RNA (siRNA) was used to modulate autophagy, and the effect of autophagy on the Dec2 pathway was explored using real‐time polymerase chain reaction and western blot analysis in vitro. Results LPS‐treated human PDLFs (HPDLFs) induced autophagy, as demonstrated by the enhanced levels of microtubule‐associated protein 1 light chain 3‐II (LC3‐II) and the induction of ATG5, Beclin1, and Dec2. Compared with a scrambled siRNA, a Dec2 siRNA triggered the detrimental influences of LPS and markedly enhanced autophagy expression in inflamed HPDLFs. The expression of phosphorylated ERK was increased and levels of phosphorylated mammalian target of rapamycin (mTOR) were decreased after exposure to LPS in Dec2 siRNA transfected HPDLFs. The Dec2KO model exhibited that P. gingivalis in Dec2 deficient conditions increases the inflammation of PDLFs by regulating autophagy. Conclusions These results demonstrate that a Dec2 deficiency can alleviate LPS‐induced inflammation via the ERK/mTOR signaling pathway by regulating autophagy, conceivably delivering a novel approach for the detection of periodontal treatments.https://doi.org/10.1002/iid3.389autophagyDec2ERK/mTOR pathwayknock‐out animal modelP. gingivalisperiodontal inflammation |
| spellingShingle | Shunichi Oka Xiaoyan Li Fuyuki Sato Fengzhu Zhang Nitesh Tewari Chongchong Chen Liangjun Zhong Makoto Makishima Yi Liu Ujjal K. Bhawal Dec2 attenuates autophagy in inflamed periodontal tissues Immunity, Inflammation and Disease autophagy Dec2 ERK/mTOR pathway knock‐out animal model P. gingivalis periodontal inflammation |
| title | Dec2 attenuates autophagy in inflamed periodontal tissues |
| title_full | Dec2 attenuates autophagy in inflamed periodontal tissues |
| title_fullStr | Dec2 attenuates autophagy in inflamed periodontal tissues |
| title_full_unstemmed | Dec2 attenuates autophagy in inflamed periodontal tissues |
| title_short | Dec2 attenuates autophagy in inflamed periodontal tissues |
| title_sort | dec2 attenuates autophagy in inflamed periodontal tissues |
| topic | autophagy Dec2 ERK/mTOR pathway knock‐out animal model P. gingivalis periodontal inflammation |
| url | https://doi.org/10.1002/iid3.389 |
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