Stem cells rescue cardiomyopathy induced by <i>P. gingivalis</i>‐LPS via miR‐181b

Chen, Tung-Sheng; Battsengel, Sarnai; Kuo, Chia Hua; Pan, Lung Fa; Yao, Chun Hsu; Chen, Yueh Sheng; Lin, Feng Huei; Kuo, Wei Wen; Huang, Chih‐Yang

doi:10.1002/jcp.26386

Cited by 11 publications

(9 citation statements)

References 18 publications

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“…Periodontitis (PD) is a bacterial infection in the tissue that supports the teeth, leading to chronic local inflammation, destruction of connective tissue and alveolar bone, and eventually loss of teeth. It is also associated with an increase of myocardial cell damage and heart failure [ 1 , 2 ]. Porphyromonas gingivalis (PG) is a gram-negative bacterial pathogen often identified in adult PD, and systemic exposure to pro-inflammatory factors from PG, including lipopolysaccharide, may contribute to CVD [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

Role of TLR4 signaling on Porphyromonas gingivalis LPS-induced cardiac dysfunction in mice

et al. 2022

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Oral infections, particularly periodontitis, are a well-established risk factor for cardiovascular diseases, although the molecular mechanisms involved remain elusive. The aims of the present study were to investigate the effects of lipopolysaccharide derived from Porphyromonas gingivalis (PG-LPS) on cardiac function in mice, and to elucidate the underlying mechanisms. Mice (C57BL/6) were injected with PG-LPS (0.8 mg/kg/day) with or without an inhibitor of Toll-like receptor 4 (TLR4) signaling (TAK-242, 0.8 mg/kg/day) for 4 weeks. Left ventricular ejection function was significantly decreased at 1 week (from 67 ± 0.5 to 58 ± 1.2%) and remained low at 4 weeks (57 ± 1.0%). The number of apoptotic myocytes was increased (approximately 7.4-fold), the area of fibrosis was increased (approximately 3.3-fold) and the number of 8-hydroxydeoxyguanosine-positive myocytes, a sensitive indicator of oxidative DNA damage, was increased (approximately 7.6-fold) at 4 weeks in the heart of PG-LPS treated mice. However, levels of various serum pro-inflammatory cytokines in PG-LPS-treated mice were similar to those in control mice. The impairment of cardiac function in PG-LPS-treated mice appears to involve activation of TLR4-NADPH oxidase (NOX) 4 signaling, leading to abundant production of reactive oxygen species and Ca2+ leakage from sarcoplastic reticulumn induced by calmodulin kinase II (CaMKII)-mediated phosphorylation of phospholamban (at Thr-17) and ryanodine receptor 2 (at Ser-2448). Pharmacological inhibition of TLR4 with TAK-242 attenuated the changes in cardiac function in PG-LPS-treated mice. Our results indicate that TLR4-NOX4 signaling may be a new therapeutic target for treatment of cardiovascular diseases in patients with periodontitis.

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Section: Introductionmentioning

confidence: 99%

Role of TLR4 signaling on Porphyromonas gingivalis LPS-induced cardiac dysfunction in mice

et al. 2022

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“…In a paper published by Lee et al (2006), it was evidenced that Porphyromonas gingivalis impairs cardiomyoblasts H9c2 through the promotion of hypertrophy factors and stimulation of the MMP9 fibrosis molecule. A previous work demonstrated that cardiomyopathy stimulated by Porphyromonas gingivalis in part includes p38 MAPK induction [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

The Beneficial Effect of Carvacrol in HL-1 Cardiomyocytes Treated with LPS-G: Anti-Inflammatory Pathway Investigations

et al. 2022

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Carvacrol (CAR), a natural phenolic monoterpene, possesses different biological activities, such as anti-inflammatory and antioxidant activities. The current study aimed to evaluate the response of HL-1 cardiomyocytes to an inflammatory stimulus triggered by lipopolysaccharide from Porphyromonas gingivalis (LPS-G), alone or in co-treatment with CAR, to investigate the potential protective role of CAR in the inflammatory process through modulation of the TLR4/NFκB/NALP3/IL-1β pathway and ROS production. In an in vitro experiment, HL-1 cardiomyocytes were exposed to LPS-G and incubated with CAR. We evaluated the anti-inflammatory effect of CAR by the reduction in TLR4, NFκB, NALP3, and IL-1β expression using immunofluorescence staining. Western blot analysis also validated the modulation of the TLR4/NFκB/NALP3/IL-1β pathway. ROS analyses confirmed the protective effects of CAR. Our results suggest that CAR could provide a significant protection role against inflammatory stimulus generated by LPS-G, involving the suppression of the TLR4/NFκB/NALP3/IL-1β signaling pathway.

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“…Total RNA was extracted using a Direct-zol™ RNA MiniPrep commercial kit (Zymo Research Corporation, CA, USA) according to the manufacturer’s protocol [ 65 , 66 ]. miRNAs were reverse transcribed to cDNA using a miRNA cDNA synthesis kit (Takara, Shiga, Japan) as described previously [ 16 , 67 ]. hsa-miR-4535 and Smad4 expression was detected by real-time PCR in a LightCycler 96 Systems (Roche, Basel, Switzerland) using the standard LightCycler 480 SYBR Green I Master protocol.…”

Section: Methodsmentioning

confidence: 99%

Protective effects of galangin against H2O2/UVB-induced dermal fibroblast collagen degradation via hsa-microRNA-4535-mediated TGFβ/Smad signaling

Lee

et al. 2021

Aging

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This study aimed to investigate the mechanism underlying the protective effects of galangin against H 2 O 2 /UVB-induced damage using in vitro and in vivo models of photodamage. Moreover, we identified the involvement of miRNA regulation in this process. The H 2 O 2 /UVB-treated HS68 human dermal fibroblasts and UVB-induced C57BL/6J nude mice were used as in vitro and in vivo models of photodamage. The results showed that galangin treatment alleviated H 2 O 2 /UVB-induced reduction in cell viability, TGFβ/Smad signaling impairment, and dermal aging. Based on the results of microRNA array analyses and database searches, hsa-miR-4535 was identified as a potential candidate miRNA that targets Smad4. In vitro , galangin treatment activated Smad2/3/4 complex and inhibited hsa-miR-4535 expression in H2O2/UVB-exposed cells. In vivo , topical application of low (12 mg/kg) and high doses (24 mg/kg) of galangin to the dorsal skin of C57BL/6J nude mice significantly alleviated UVB-induced skin photodamage by promoting TGFβ/Smad collagen synthesis signaling, reducing epidermal hyperplasia, wrinkle formation, and skin senescence, as well as inhibiting hsa-miR-4535 expression. Taken together, our findings indicate a link between hsa-miR-4535 and TGFβ/Smad collagen synthesis signaling and suggest these factors to be involved in the photo-protective mechanism of galangin in dermal fibroblasts against H 2 O 2 /UVB-induced aging. The evidence indicated that galangin with anti-aging properties can be considered as a supplement in skin care products.

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Stem cells rescue cardiomyopathy induced by P. gingivalis‐LPS via miR‐181b

Cited by 11 publications

References 18 publications

Role of TLR4 signaling on Porphyromonas gingivalis LPS-induced cardiac dysfunction in mice

Role of TLR4 signaling on Porphyromonas gingivalis LPS-induced cardiac dysfunction in mice

The Beneficial Effect of Carvacrol in HL-1 Cardiomyocytes Treated with LPS-G: Anti-Inflammatory Pathway Investigations

Protective effects of galangin against H2O2/UVB-induced dermal fibroblast collagen degradation via hsa-microRNA-4535-mediated TGFβ/Smad signaling

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