MiR-146a-5p promotes IL-1β-induced chondrocyte apoptosis through the TRAF6-mediated NF-kB pathway

Shao, Jiahua; Ding, Zheru; Peng, Jie; Zhou, Rong; Li, Lexiang; Qian, Qirong; Chen, Yi

doi:10.1007/s00011-020-01346-w

Cited by 44 publications

(34 citation statements)

References 34 publications

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“…In this study, miR-146a-5p was shown to be upregulated in IL-1b-stimulated SW1353 and C28/I2 cells, and miR-146a-5p knockdown significantly promoted proliferation and inhibited apoptosis and the expression of inflammatory factors in both cell types. The observed expression of miR-146a-5p is consistent with previous clinical findings, 25 and with the report that miR-146a-5p promotes chondrocyte apoptosis induced by IL-1b, 27 suggesting the potential of miR-146a-5p as a regulator of OA injury.…”

Section: Discussionsupporting

confidence: 91%

Effects of miR-146a-5p on chondrocyte interleukin-1β-induced inflammation and apoptosis involving thioredoxin interacting protein regulation

Zhao

2020

J Int Med Res

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Objective Osteoarthritis (OA) is a chronic degenerative arthropathy characterized by articular cartilage degeneration, subchondral osteosclerosis, and hyperosteogeny. MicroRNAs (miRNAs) play an important regulatory role in its pathological development, so this study explored the effect and potential mechanism of miR-146a-5p in interleukin (IL)-1β-induced OA cartilage injury. Methods The human chondrosarcoma cell line SW1353 and normal human chondrocytes C28/I2 were stimulated by IL-1β to construct the OA chondrocyte model. miR-146a-5p and thioredoxin interacting protein (TXNIP) expression levels were detected by quantitative real-time (qRT)-PCR and western blot. Their expression was modified by transfecting an miR-146a-5p inhibitor, mimic, and pcDNA-TXNIP. The relationship between miR-146a-5p and TXNIP was analyzed by the dual-luciferase assay, while cell viability, apoptosis, and inflammatory expression were determined by cell counting, TUNEL staining, and ELISA, respectively. Results miR-146a-5p expression was upregulated in SW1353 and C28/I2 cells stimulated by IL-1β. miR-146a-5p knockdown significantly enhanced cell activity, inhibited inflammatory factor expression, and reduced cell apoptosis. The dual-luciferase assay revealed TXNIP as a target gene of miR-146a-5p and suggested that miR-146a-5p promotion of OA damage could be reversed by upregulating TXNIP. Conclusion These results suggest that miR-146a-5p inhibits cell proliferation and promotes apoptosis and the inflammatory response in OA cartilage injury by modulating TXNIP.

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Section: Discussionsupporting

confidence: 91%

Effects of miR-146a-5p on chondrocyte interleukin-1β-induced inflammation and apoptosis involving thioredoxin interacting protein regulation

Zhao

2020

J Int Med Res

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“…Therefore, TRAF6 has a positive regulatory effect on fat accumulation. Importantly, the NF-κB signaling which was the TRAF6 downstream inhibited in ammatory injury, promoted chondrocyte apoptosis and repressing pancreatic cancer cell proliferation [24,41,42]. In this study, we uncovered that miR-146a-5p targeting TRAF6 inhibited differentiation of porcine intramuscular preadipocytes by NF-κB signaling pathway.…”

Section: Discussionmentioning

confidence: 80%

MiR-146a-5p Targeting SMAD4 and TRAF6 Inhibits Adipogenensis Through TGF-β and NF-κB Signal Pathways in Porcine Intramuscular Preadipocytes

Zhang

Cai

Tang

et al. 2020

Preprint

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Background: Intramuscular fat (IMF) content is a vital parameter to assess pork quality. Increasing evidences have shown that microRNAs (miRNAs) play an important role in regulating porcine IMF deposition. Here, a novel miRNA implicated in porcine IMF adipogenesis was found, and its effect and regulatory mechanism was further explored on the proliferation and differentiation of intramuscular preadipocytes.Results: By miRNAs sequencing analysis in porcine adipose tissues, we found that miR-146a-5p was a potential regulator of porcine IMF adipogenesis. Further study showed that miR-146a-5p mimics inhibited the proliferation of porcine intramuscular preadipocytes, but its inhibitor promoted cell proliferation. Interestingly, miR-146a-5p mimics also repressed preadipocyte differentiation, whereas its inhibitor promoted adipogenic differentiation. Mechanistically, miR-146a-5p suppressed cell proliferation by directly targeting SMAD family member 4 (SMAD4) to attenuate the TGF-β signal. Moreover, miR-146a-5p inhibited the differentiation of intramuscular preadipocytes by targeting TNF receptor associated factor 6 (TRAF6) to weaken the NF-κB signaling of the TRAF6 downstream pathway.Conclusions: MiR-146a-5p targeting SMAD4 and TRAF6 inhibited porcine intramuscular adipogenesis through attenuating TGF-β and NF-κB signals, respectively. These findings provided a novel miRNA biomarker for regulating intramuscular adipogenesis to promote pork quality.

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“…Mathilde et al reported apoptosis was elicited through NF-κB pathway in cystic brosis cells [48] . Shao et al also showed miR-146a-5p promoted IL-1β-induced chondrocyte apoptosis via the TRAF6-mediated NF-kB pathway [49] . On the contrary, Robert E et al have demonstrated NF-κB activation after T. gondii RH strain infection is involved in the increase of anti-apoptotic gene expression, which plays a pivotal role in the T.…”

Section: Discussionmentioning

confidence: 97%

Toxoplasma gondii Chinese 1 Genotype Wh6 Strain Causes Mice Abnormal Cognitive Behavior through Affecting Hippocampal Neurons

Tao

Cui

Liu

et al. 2020

Preprint

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BackgroundChronic Toxoplasma gondii (T. gondii) infection evokes abnormal cognitive behavior of the host. Recent studies suggest that the polarization of microglia to the phenotype of classically activated macrophage (M1) and the deposition of beta-amyloid (Aβ) may be induced in brain of mice chronically infected with T. gondii. However, so far, there is no definite explanation for the relationship mechanism underlying the above between microglia polarization, Aβ deposition and T. gondii. Our previous investigations indicated that in vitro T. gondii type Ⅱ strain dense granule protein 15 (GRA15Ⅱ), one of the genotype-associated effectors of T. gondii Ⅱ strain may induce mouse macrophage to M1. While T. gondii type Ⅰ/Ⅲ strain rhoptry protein 16 (ROP16Ⅰ/Ⅲ) can drive the mouse macrophage to the phenotype of alternatively activated macrophage (M2). Unlike the archetypal strains of types Ⅰ, Ⅱ, and Ⅲ, T. gondii Chinese 1 genotype Wh6 strain (TgCtwh6) possesses both GRA15Ⅱ and ROP16Ⅰ/Ⅲ proteins, indicating the unique pathogenesis of Toxoplasma-related cognitive behavioral abnormalities.MethodsIn this study, we constructed mice model of cognitive behavioral abnormalities through chronic infection of TgCtwh6 via the oral route, and used mouse hippocampal neuronal cell line (HT22) and mouse microglial cell line (BV2) infected with TgCtwh6 in co-culture system to explore the mechanism with which TgCtwh6 infection induced mouse abnormal cognitive behavior. The immunohistochemistry, immunofluorescence, western blotting, cell culture assays, as well as an array of mouse behavior tests were adopted in the research.ResultsIn our research, the infected group showed abnormal cognitive behavior in the water maze and open field experiments in comparison with the control group. Further study showed that the number of synapses and hippocampal neurons decreased and the expression of Aβ increased in brain. In vitro, our research indicated that TgCtwh6 infection could not only directly lead to the HT22 apoptosis but also directly induce BV2 activation to M1 possibly through Notch pathway. Activated BV2 secreted pro-inflammatory factors resulting in HT22 apoptosis indirectly in transwell device. Meanwhile, our reseach demonstrated that TgCtwh6 infection caused a notable expression of β-secretase 1 (BACE1)、amyloid precursor protein (APP) and Aβ in HT22 through NF-κB signaling. Furthmore, BV2 activated by TgCtwh6 infection produced pro-inflammatory factors, such as IL-6, TNF-α and iNOS, which promoted HT22 to express APP in co-culture system. In all, our results suggested that TgCtwh6 gave rise to mouse abnormal cognitive behavior due to hippocampal neuronal apoptosis and Aβ deposition driven by indirect and indirect TgCtwh6 infection to hippocampal neuron. In this pathogenic process, microglia activation played an important role in mediating hippocampal neuronal apoptosis and Aβ deposition.ConclusionsThis study demonstrates TgCtwh6 infection can cause mice to develop AD-like symptoms and give rise to hippocampal neuronal apoptosis and Aβ deposition. Besides, microglia activation played an functional role in the pathological development.

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MiR-146a-5p promotes IL-1β-induced chondrocyte apoptosis through the TRAF6-mediated NF-kB pathway

Cited by 44 publications

References 34 publications

Effects of miR-146a-5p on chondrocyte interleukin-1β-induced inflammation and apoptosis involving thioredoxin interacting protein regulation

Effects of miR-146a-5p on chondrocyte interleukin-1β-induced inflammation and apoptosis involving thioredoxin interacting protein regulation

MiR-146a-5p Targeting SMAD4 and TRAF6 Inhibits Adipogenensis Through TGF-β and NF-κB Signal Pathways in Porcine Intramuscular Preadipocytes

Toxoplasma gondii Chinese 1 Genotype Wh6 Strain Causes Mice Abnormal Cognitive Behavior through Affecting Hippocampal Neurons

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MiR-146a-5p promotes IL-1β-induced chondrocyte apoptosis through the TRAF6-mediated NF-kB pathway

Cited by 44 publications

References 34 publications

Effects of miR-146a-5p on chondrocyte interleukin-1β-induced inflammation and apoptosis involving thioredoxin interacting protein regulation

Effects of miR-146a-5p on chondrocyte interleukin-1β-induced inflammation and apoptosis involving thioredoxin interacting protein regulation

MiR-146a-5p Targeting SMAD4 and TRAF6 Inhibits Adipogenensis Through TGF-β and NF-κB Signal Pathways in Porcine Intramuscular Preadipocytes

Toxoplasma gondii&nbsp;Chinese 1 Genotype Wh6 Strain Causes Mice Abnormal Cognitive Behavior through Affecting Hippocampal Neurons

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Toxoplasma gondii Chinese 1 Genotype Wh6 Strain Causes Mice Abnormal Cognitive Behavior through Affecting Hippocampal Neurons