Loss of Dec1 prevents autophagy in inflamed periodontal ligament fibroblast

• Published in: Molecular biology reports 2021-02, Vol.48 (2), p.1423-1431
• Main Authors: Oka, Shunichi, Li, Xiaoyan, Zhang, Fengzhu, Tewari, Nitesh, Kim, Il-Shin, Chen, Chongchong, Zhong, Liangjun, Hamada, Nobushiro, Oi, Yoshiyuki, Makishima, Makoto, Liu, Yi, Bhawal, Ujjal K.
• Format: Article
• Language: English
• Subjects: AKT protein; Animal Anatomy; Animal Biochemistry; Animals; Autophagy; Autophagy - genetics; Autophagy-Related Protein 5 - genetics; Basic Helix-Loop-Helix Transcription Factors - antagonists & inhibitors; Basic Helix-Loop-Helix Transcription Factors - genetics; Beclin-1 - genetics; Biomedical and Life Sciences; Fibroblasts; Fibroblasts - metabolism; Fibroblasts - pathology; Gene Expression Regulation - genetics; Histology; Homeodomain Proteins - antagonists & inhibitors; Homeodomain Proteins - genetics; Homeostasis; Humans; IL-1β; Inflammation; Inflammation - chemically induced; Inflammation - genetics; Inflammation - pathology; Life Sciences; Ligaments; Lipopolysaccharides; Lipopolysaccharides - toxicity; Mice; Mice, Knockout; Microtubule-associated protein 1; Microtubule-Associated Proteins - genetics; Morphology; Original Article; Periodontal ligament; Periodontal Ligament - metabolism; Periodontal Ligament - microbiology; Periodontal Ligament - pathology; Phagocytosis; Polymerase chain reaction; Porphyromonas gingivalis - pathogenicity; Proto-Oncogene Proteins c-akt - genetics; RNA, Small Interfering - genetics; RNA, Small Interfering - pharmacology; Signal transduction; Signal Transduction - genetics; siRNA; TOR protein; TOR Serine-Threonine Kinases - genetics; Tumor Suppressor Proteins - genetics
• ISSN: 0301-4851; 1573-4978
• DOI: 10.1007/s11033-021-06162-x

Periodontal ligament fibroblasts (PDLFs) are integral to the homeostasis of periodontal tissue. The transcription factor Dec1 functions to modulate Porphyromonas gingivalis -induced periodontal inflammation. Here, we aimed to characterize the Dec1-mediated autophagy in PDLFs under inflammatory conditions. Human PDLFs were subjected to an inflammatory environment using P. gingivalis Lipopolysaccaride (LPS) along with Dec1 siRNA in vitro. Quantitative real-time polymerase chain reaction and Western blot analyses were used to evaluate the expression levels of autophagy-related genes and their upstream AKT/mTOR signaling pathways. An experimental P. gingivalis -treated Dec1 knockout ( Dec1 KO) mouse model was used to confirm the expression of autophagy in PDLFs in vivo. Treatment with P. gingivalis LPS induced the expression of ATG5, Beclin1 and microtubule-associated protein 1 light chain 3 (LC3) and elevated the expression of pro-inflammatory cytokine IL-1β and Dec1 in human PDLFs. Knockdown of Dec1 partly reversed the detrimental influences of LPS on these autophagy markers in human PDLFs. The inhibition of autophagy with Dec1 siRNA suppressed the inflammatory effect of AKT/mTOR signaling pathways following treatment with P. gingivalis LPS. P. gingivalis -treated Dec1 KO mice partly reduced autophagy expression. These findings suggest that a Dec1 deficiency can modulate the interaction between autophagy and inflammation in PDLFs.