MiR-423-5P Regulates Cells Apoptosis and Extracellular Matrix Degradation via Nucleotide-Binding, Leucine-Rich Repeat Containing X1 (NLRX1) in Interleukin 1 beta (IL-1β)-Induced Human Nucleus Pulposus Cells

Hu, Xu; Ji, Liefeng; Yu, Chunhua; Chen, Qiming; Ge, Qiangqiang; Lu, Yinjiang

doi:10.12659/msm.922497

Cited by 7 publications

(7 citation statements)

References 32 publications

(31 reference statements)

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“…NLRX1 has been shown to affect both. Overexpression of NLRX1 human nucleus pulposus cells in the intervertebral disc resulted in increased collagen synthesis and decreased ECM decomposing enzymes ( 103 ). On the other hand, Nlrx1- deficiency led to increased expression of wound healing factors epidermal growth factor (EGF) and TGFβ in epithelial cells in a mouse model of DSS-induced colitis ( 104 ).…”

Section: Discussionmentioning

confidence: 99%

Sex-Biased Control of Inflammation and Metabolism by a Mitochondrial Nod-Like Receptor

et al. 2022

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Mitochondria regulate steroid hormone synthesis, and in turn sex hormones regulate mitochondrial function for maintaining cellular homeostasis and controlling inflammation. This crosstalk can explain sex differences observed in several pathologies such as in metabolic or inflammatory disorders. Nod-like receptor X1 (NLRX1) is a mitochondria-associated innate receptor that could modulate metabolic functions and attenuates inflammatory responses. Here, we showed that in an infectious model with the human protozoan parasite, Leishmania guyanensis, NLRX1 attenuated inflammation in females but not in male mice. Analysis of infected female and male bone marrow derived macrophages showed both sex- and genotype-specific differences in both inflammatory and metabolic profiles with increased type I interferon production, mitochondrial respiration, and glycolytic rate in Nlrx1-deficient female BMDMs in comparison to wild-type cells, while no differences were observed between males. Transcriptomics of female and male BMDMs revealed an altered steroid hormone signaling in Nlrx1-deficient cells, and a “masculinization” of Nlrx1-deficient female BMDMs. Thus, our findings suggest that NLRX1 prevents uncontrolled inflammation and metabolism in females and therefore may contribute to the sex differences observed in infectious and inflammatory diseases.

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Section: Discussionmentioning

confidence: 99%

Sex-Biased Control of Inflammation and Metabolism by a Mitochondrial Nod-Like Receptor

et al. 2022

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“…We found a three-fold downregulation in the expression of miR-423-5p in the BALF-derived exosomes from COPD patients as compared to healthy non-smoking controls. Of note, miR-423-5p is known to be involved in the regulation of apoptosis and extracellular matrix degradation in human nucleus pulposus cells [ 40 ]. Contrary to our findings, Molina-Pinelo et al (2014) identified increased expression of miR-423-5p in the BALF collected from COPD patients as compared to the control group.…”

Section: Discussionmentioning

confidence: 99%

Distinct Exosomal miRNA Profiles from BALF and Lung Tissue of COPD and IPF Patients

Kaur

Maremanda

Campos

et al. 2021

IJMS

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Chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) are chronic, progressive lung ailments that are characterized by distinct pathologies. Early detection biomarkers and disease mechanisms for these debilitating diseases are lacking. Extracellular vesicles (EVs), including exosomes, are small, lipid-bound vesicles attributed to carry proteins, lipids, and RNA molecules to facilitate cell-to-cell communication under normal and diseased conditions. Exosomal miRNAs have been studied in relation to many diseases. However, there is little to no knowledge regarding the miRNA population of bronchoalveolar lavage fluid (BALF) or the lung-tissue-derived exosomes in COPD and IPF. Here, we determined and compared the miRNA profiles of BALF- and lung-tissue-derived exosomes of healthy non-smokers, smokers, and patients with COPD or IPF in independent cohorts. Results: Exosome characterization using NanoSight particle tracking and TEM demonstrated that the BALF-derived exosomes were ~89.85 nm in size with a yield of ~2.95 × 1010 particles/mL in concentration. Lung-derived exosomes were larger in size (~146.04 nm) with a higher yield of ~2.38 × 1011 particles/mL. NGS results identified three differentially expressed miRNAs in the BALF, while there was one in the lung-derived exosomes from COPD patients as compared to healthy non-smokers. Of these, miR-122-5p was three- or five-fold downregulated among the lung-tissue-derived exosomes of COPD patients as compared to healthy non-smokers and smokers, respectively. Interestingly, there were a large number (55) of differentially expressed miRNAs in the lung-tissue-derived exosomes of IPF patients compared to non-smoking controls. Conclusions: Overall, we identified lung-specific miRNAs associated with chronic lung diseases that can serve as potential biomarkers or therapeutic targets.

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“…We found a 3-fold downregulation in the expression of miR-423-5p in the BALF-derived exosomes from COPD patients as compared to healthy non-smoking controls. Of note, miR-423-5p is known to be involved in the regulation of apoptosis and extracellular matrix degradation in human nucleus pulposus cells (44). Contrary to our findings, Molina-Pinelo et al (2014) identified increased expression of miR-423-5p in the BALF collected from COPD patients as compared to the control group.…”

Section: Discussionmentioning

confidence: 99%

Distinct exosomal miRNA profiles from BALF and lung tissue from COPD and IPF patients

Kaur

Maremanda

Campos

et al. 2021

Preprint

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BackgroundChronic Obstructive Pulmonary Disease (COPD) and Idiopathic Pulmonary Fibrosis (IPF) are chronic, progressive lung ailments which are characterized by distinct pathologies. Early detection biomarkers and disease mechanisms for these debilitating diseases are lacking. Exosomes are small extracellular vesicles attributed to carry proteins, mRNA, miRNA and sncRNA to facilitate cell-to-cell communication under normal and diseased conditions. Exosomal miRNAs have been studied in relation to many diseases. However, there is little to no knowledge regarding the miRNA population of BALF or the lung tissue derived exosomes in COPD and IPF. Here, we determined and compared the miRNA profiles of BALF and lung tissue-derived exosomes from healthy non-smokers, healthy smokers, and patients with COPD and IPF in independent cohorts.ResultsExosome characterization using NanoSight particle tracking and TEM demonstrated that the BALF-derived exosomes were approximately 89.85 nm in size and ∼2.95 × 1010 particles/mL. Lung-derived exosomes were ∼146.04 nm in size and ∼2.38 × 1011 particles/mL. NGS results identified three differentially expressed miRNAs in the BALF, while one in the lung-derived exosomes from COPD patients as compared to healthy non-smokers. Of these, three- and five-fold downregulation of miR-122-5p amongst the lung tissue-derived exosomes from COPD patients as compared to healthy non-smokers and smokers, respectively. Interestingly, there were key 55 differentially expressed miRNAs in the lung tissue-derived exosomes of IPF patients compared to non-smoking controls.ConclusionsOverall, we identified specific miRNAs to develop as biomarkers or targets for pathogenesis of these chronic lung diseases.

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MiR-423-5P Regulates Cells Apoptosis and Extracellular Matrix Degradation via Nucleotide-Binding, Leucine-Rich Repeat Containing X1 (NLRX1) in Interleukin 1 beta (IL-1β)-Induced Human Nucleus Pulposus Cells

Cited by 7 publications

References 32 publications

Sex-Biased Control of Inflammation and Metabolism by a Mitochondrial Nod-Like Receptor

Sex-Biased Control of Inflammation and Metabolism by a Mitochondrial Nod-Like Receptor

Distinct Exosomal miRNA Profiles from BALF and Lung Tissue of COPD and IPF Patients

Distinct exosomal miRNA profiles from BALF and lung tissue from COPD and IPF patients

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