PMID- 35730318
OWN - NLM
STAT- MEDLINE
DCOM- 20240130
LR  - 20240130
IS  - 1601-0825 (Electronic)
IS  - 1354-523X (Linking)
VI  - 29
IP  - 8
DP  - 2023 Nov
TI  - PINK1-mediated mitophagy reduced inflammatory responses to Porphyromonas 
      gingivalis in macrophages.
PG  - 3665-3676
LID - 10.1111/odi.14286 [doi]
AB  - OBJECTIVE: Mitochondria are strained by microbial stimuli in the periodontal 
      niche. Damaged mitochondria are cleared by mitophagy. The purpose of the study 
      was to explore whether mitophagy participated in the progress of periodontitis 
      and whether activation of mitophagy can inhibit inflammatory responses to 
      bacterial infection in macrophages. METHODS: Mitophagy-related genes were 
      measured in the healthy and inflamed human gingiva. Bone marrow-derived 
      macrophages (BMDMs) were infected with Porphyromonas gingivalis. Dexmedetomidine, 
      urolithin A, and resveratrol were used to activate mitophagy, while small 
      interference RNA was utilized to knock down PTEN-induced putative protein kinase 
      1 (PINK1). Activation of mitophagy-related genes and colocalization of them were 
      detected by Western blot and confocal imaging. Damages of mitochondria, 
      accumulation of mitochondrial reactive oxygen species (mtROS), and production of 
      IL-1beta, IL-6, and TNF-alpha were measured. RESULTS: Levels of mitophagy-related genes 
      were decreased in inflamed periodontal tissues and P. gingivalis-infected BMDMs. 
      Dexmedetomidine, urolithin A, and resveratrol activated mitophagy, leading to 
      reduced mitochondria damages, decreased mtROS generation, and inhibited IL-1beta, 
      IL-6, and TNF-alpha production. PINK1 knockdown reduced dexmedetomidine, urolithin A, 
      and resveratrol-induced anti-inflammatory effect. CONCLUSION: Inhibited mitophagy 
      participated in the progress of periodontitis. Activation of mitophagy may become 
      a therapeutic target during the progress of periodontitis by reducing mtROS.
CI  - (c) 2022 Wiley Periodicals LLC.
FAU - Jiang, Ke
AU  - Jiang K
AD  - Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, 
      China.
AD  - Central Laboratory of Stomatology, Nanjing Stomatological Hospital, Medical 
      School of Nanjing University, Nanjing, China.
FAU - Li, Jingwen
AU  - Li J
AD  - Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, 
      China.
AD  - Central Laboratory of Stomatology, Nanjing Stomatological Hospital, Medical 
      School of Nanjing University, Nanjing, China.
FAU - Jiang, Lishan
AU  - Jiang L
AD  - Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, 
      China.
AD  - Central Laboratory of Stomatology, Nanjing Stomatological Hospital, Medical 
      School of Nanjing University, Nanjing, China.
FAU - Li, Houxuan
AU  - Li H
AUID- ORCID: 0000-0002-3798-8628
AD  - Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, 
      China.
FAU - Lei, Lang
AU  - Lei L
AUID- ORCID: 0000-0003-2892-040X
AD  - Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, 
      China.
LA  - eng
GR  - 2019060009/Nanjing Clinical Research Center for Oral Diseases/
GR  - ZKX200047/Nanjing Medical Science and Technique Development Foundation/
GR  - 81670996/National Natural Science Foundation of China/
PT  - Journal Article
DEP - 20220712
PL  - Denmark
TA  - Oral Dis
JT  - Oral diseases
JID - 9508565
RN  - 67VB76HONO (Dexmedetomidine)
RN  - 0 (Interleukin-6)
RN  - EC 2.7.- (Protein Kinases)
RN  - Q369O8926L (Resveratrol)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 2.7.11.1 (PTEN-induced putative kinase)
MH  - Humans
MH  - *Dexmedetomidine/pharmacology
MH  - Interleukin-6
MH  - Macrophages/metabolism
MH  - *Mitophagy
MH  - *Periodontitis
MH  - *Porphyromonas gingivalis/metabolism
MH  - Protein Kinases/genetics/metabolism
MH  - Resveratrol/pharmacology
MH  - Tumor Necrosis Factor-alpha/metabolism
OTO - NOTNLM
OT  - PINK1
OT  - inflammation
OT  - mitochondria
OT  - mitophagy
OT  - periodontitis
OT  - reactive oxygen species
EDAT- 2022/06/23 06:00
MHDA- 2023/12/07 12:42
CRDT- 2022/06/22 04:03
PHST- 2022/06/08 00:00 [revised]
PHST- 2022/03/29 00:00 [received]
PHST- 2022/06/14 00:00 [accepted]
PHST- 2023/12/07 12:42 [medline]
PHST- 2022/06/23 06:00 [pubmed]
PHST- 2022/06/22 04:03 [entrez]
AID - 10.1111/odi.14286 [doi]
PST - ppublish
SO  - Oral Dis. 2023 Nov;29(8):3665-3676. doi: 10.1111/odi.14286. Epub 2022 Jul 12.