PMID- 33270996
OWN - NLM
STAT- MEDLINE
DCOM- 20211015
LR  - 20211015
IS  - 2050-4527 (Electronic)
IS  - 2050-4527 (Linking)
VI  - 9
IP  - 1
DP  - 2021 Mar
TI  - Dec2 attenuates autophagy in inflamed periodontal tissues.
PG  - 265-273
LID - 10.1002/iid3.389 [doi]
AB  - 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.
CI  - (c) 2020 The Authors. Immunity, Inflammation and Disease published by John Wiley & 
      Sons Ltd.
FAU - Oka, Shunichi
AU  - Oka S
AD  - Department of Anesthesiology, Nihon University School of Dentistry, Tokyo, Japan.
AD  - Division of Immunology and Pathology, Dental Research Center, Nihon University 
      School of Dentistry, Tokyo, Japan.
FAU - Li, Xiaoyan
AU  - Li X
AUID- ORCID: 0000-0001-7166-0135
AD  - Laboratory 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 China.
FAU - Sato, Fuyuki
AU  - Sato F
AD  - Pathology Division, Shizuoka Cancer Center, Shizuoka, Japan.
FAU - Zhang, Fengzhu
AU  - Zhang F
AD  - Department of Anesthesiology, Nihon University School of Dentistry at Matsudo, 
      Chiba, Japan.
FAU - Tewari, Nitesh
AU  - Tewari N
AD  - Division of Pedodontics and Preventive Dentistry, Centre for Dental Education and 
      Research, All India Institute of Medical Sciences, New Delhi, India.
FAU - Chen, Chongchong
AU  - Chen C
AD  - Department of Stomatology, Hangzhou Normal University, Hangzhou, People's 
      Republic of China.
FAU - Zhong, Liangjun
AU  - Zhong L
AD  - Department of Stomatology, Hangzhou Normal University, Hangzhou, People's 
      Republic of China.
FAU - Makishima, Makoto
AU  - Makishima M
AD  - Division of Biochemistry, Department of Biomedical Sciences, Nihon University 
      School of Medicine, Tokyo, Japan.
FAU - Liu, Yi
AU  - Liu Y
AD  - Laboratory 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 China.
FAU - Bhawal, Ujjal K
AU  - Bhawal UK
AUID- ORCID: 0000-0002-3746-009X
AD  - Department of Disaster Medicine and Dental Sociology, Kanagawa Dental University, 
      Yokosuka, Japan.
AD  - Department of Biochemistry and Molecular Biology, Nihon University School of 
      Dentistry at Matsudo, Chiba, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20201203
PL  - England
TA  - Immun Inflamm Dis
JT  - Immunity, inflammation and disease
JID - 101635460
RN  - 0 (Lipopolysaccharides)
SB  - IM
MH  - Animals
MH  - Autophagy
MH  - Cells, Cultured
MH  - Lipopolysaccharides
MH  - Mice
MH  - *Periodontal Ligament
MH  - *Porphyromonas gingivalis
PMC - PMC7860609
OTO - NOTNLM
OT  - Dec2
OT  - ERK/mTOR pathway
OT  - P. gingivalis
OT  - autophagy
OT  - knock-out animal model
OT  - periodontal inflammation
COIS- The authors declare that there are no conflict of interests.
EDAT- 2020/12/04 06:00
MHDA- 2021/10/16 06:00
PMCR- 2020/12/03
CRDT- 2020/12/03 17:18
PHST- 2020/10/22 00:00 [received]
PHST- 2020/11/18 00:00 [revised]
PHST- 2020/11/20 00:00 [accepted]
PHST- 2020/12/04 06:00 [pubmed]
PHST- 2021/10/16 06:00 [medline]
PHST- 2020/12/03 17:18 [entrez]
PHST- 2020/12/03 00:00 [pmc-release]
AID - IID3389 [pii]
AID - 10.1002/iid3.389 [doi]
PST - ppublish
SO  - Immun Inflamm Dis. 2021 Mar;9(1):265-273. doi: 10.1002/iid3.389. Epub 2020 Dec 3.