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Updated: Jul 23, 2025
Author Spotlight: Insight Into Advances in Prion Diseases Research
Published on: August 11, 2023
Effect of mesencephalic astrocyte-derived neurotrophic factor on the inflammatory response in human gingival
Lei Gong1, Jie Dong1, Kai Huang2
1Department of Laboratory Center, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong, China.
Abstract:
Mesencephalic astrocyte-derived neurotrophic factor (MANF) is a unique member of the neurotrophic factor family residing in the endoplasmic reticulum, where it functions as a stress response protein maintaining endoplasmic reticulum homeostasis, in addition to being secreted extracellularly as a neurotrophic factor to bind with receptors to initiate intracellular signal transduction pathways. Interestingly, MANF has shown an important protective role in the inflammatory response of many diseases. In neural stem cells, pancreatic β cells, and retinal cells, MANF can inhibit the inflammatory response, modulate the immune response, and promote tissue repair. However, the role of MANF in the periodontal inflammatory response remains unclear. In the present study, we used lipopolysaccharide (LPS) from Porphyromonas gingivalis (Pg) to establish a Pg-LPS-stimulated periodontal inflammatory model in human gingival fibroblasts cells (HGF-1) to investigate the role of MANF in vitro. We found that MANF could inhibit pro-inflammatory cytokine secretion, alleviate the endoplasmic reticulum stress response, promote cell survival, and inhibit cell apoptosis. Therefore, MANF might be a novel promising target for the treatment of periodontitis.
Insights
Mesencephalic astrocyte-derived neurotrophic factor (MANF) protects against periodontal inflammation by reducing pro-inflammatory cytokines and endoplasmic reticulum stress. This suggests MANF is a potential therapeutic target for periodontitis treatment.
Area of Science:
- Cell Biology
- Immunology
- Periodontology
Background:
- Mesencephalic astrocyte-derived neurotrophic factor (MANF) is an endoplasmic reticulum-resident protein with known protective roles in inflammatory responses across various cell types.
- MANF's function involves maintaining endoplasmic reticulum homeostasis and acting as an extracellular neurotrophic factor.
- The specific role of MANF in the context of periodontal inflammation remains largely unexplored.
Purpose of the Study:
- To investigate the role of MANF in the inflammatory response within human gingival fibroblasts (HGF-1) using a Porphyromonas gingivalis lipopolysaccharide (Pg-LPS) model.
- To determine if MANF can modulate key inflammatory pathways and cellular responses in a periodontal inflammatory setting.
Main Methods:
- Establishment of an in vitro periodontal inflammatory model using human gingival fibroblasts (HGF-1) stimulated with Pg-LPS.
- Assessment of MANF's effects on pro-inflammatory cytokine secretion, endoplasmic reticulum stress markers, cell survival, and apoptosis.
Main Results:
- MANF significantly inhibited the secretion of pro-inflammatory cytokines in response to Pg-LPS.
- MANF treatment alleviated endoplasmic reticulum stress within the stimulated HGF-1 cells.
- MANF demonstrated a protective effect by promoting cell survival and inhibiting apoptosis.
Conclusions:
- MANF exhibits significant anti-inflammatory and cytoprotective properties in a model of periodontal inflammation.
- MANF may serve as a novel therapeutic target for the treatment of periodontitis.
- Further research into MANF's mechanisms in periodontal disease is warranted.
