M2a Macrophage-Secreted CHI3L1 Promotes Extracellular Matrix Metabolic Imbalances via Activation of IL-13Rα2/MAPK Pathway in Rat Intervertebral Disc Degeneration

Li, Long; Wei, Kang; Ding, Yifan; Ahati, Paerxiati; Xu, Haoran; Huang, Fang; Wang, Huan

doi:10.3389/fimmu.2021.666361

Cited by 32 publications

(40 citation statements)

References 37 publications

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“…M2a macrophages are induced by IL-4 and IL-13. They can secrete IL-10, CCL13, CCL17, and CCL22 and contribute to anti-inflammation through a TH2-like immune response and promote wound healing and induce tissue fibrosis [ 41 , 42 , 43 ]. M2b macrophages are stimulated by immune complexes and Toll-like receptors (TLR) and/or IL-1R ligands, participate in immunoregulation, and contribute to TH2-like activation.…”

Section: The Key Point Of Macrophage Multifunction: Heterogeneity And...mentioning

confidence: 99%

Reprogramming Metabolism of Macrophages as a Target for Kidney Dysfunction Treatment in Autoimmune Diseases

Tian

Chen

Zhang

et al. 2022

IJMS

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Chronic kidney disease (CKD), as one of the main complications of many autoimmune diseases, is difficult to cure, which places a huge burden on patients’ health and the economy and poses a great threat to human health. At present, the mainstream view is that autoimmune diseases are a series of diseases and complications caused by immune cell dysfunction leading to the attack of an organism’s tissues by its immune cells. The kidney is the organ most seriously affected by autoimmune diseases as it has a very close relationship with immune cells. With the development of an in-depth understanding of cell metabolism in recent years, an increasing number of scientists have discovered the metabolic changes in immune cells in the process of disease development, and we have a clearer understanding of the characteristics of the metabolic changes in immune cells. This suggests that the regulation of immune cell metabolism provides a new direction for the treatment and prevention of kidney damage caused by autoimmune diseases. Macrophages are important immune cells and are a double-edged sword in the repair process of kidney injury. Although they can repair damaged kidney tissue, over-repair will also lead to the loss of renal structural reconstruction function. In this review, from the perspective of metabolism, the metabolic characteristics of macrophages in the process of renal injury induced by autoimmune diseases are described, and the metabolites that can regulate the function of macrophages are summarized. We believe that treating macrophage metabolism as a target can provide new ideas for the treatment of the renal injury caused by autoimmune diseases.

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Section: The Key Point Of Macrophage Multifunction: Heterogeneity And...mentioning

confidence: 99%

Reprogramming Metabolism of Macrophages as a Target for Kidney Dysfunction Treatment in Autoimmune Diseases

Tian

Chen

Zhang

et al. 2022

IJMS

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“…In this study, HNPCs were cultured and stimulated with TNF-α with or without scutellarin treatment. Thereafter, phosphorylation of critical parameters in the NF-κB signaling pathway p65 ( Chen et al, 2019 ) and components of the MAPK signaling pathway ( Li L. et al, 2021 ), including JNK, p38, and ERK1/2, were assayed through Western blotting. As shown in Figures 7A–E , phosphorylated p65 was enhanced by TNF-α, which was largely abolished by additional treatment with scutellarin.…”

Section: Resultsmentioning

confidence: 99%

Scutellarin Protects Against Mitochondrial Reactive Oxygen Species-Dependent NLRP3 Inflammasome Activation to Attenuate Intervertebral Disc Degeneration

Wang

Zhang

Zhao

et al. 2022

Front. Bioeng. Biotechnol.

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Intervertebral disc degeneration (IVDD) is a predominant cause of disc herniation and is widespread worldwide. Inflammatory responses, mitochondrial dysfunction, and extracellular matrix degradation are known to be involved in IVDD. Scutellarin, an active ingredient extracted from Erigeron breviscapus (Vaniot) Ha, Hand-Mazz, is reported to exhibit therapeutic potential in several degenerative diseases by suppressing inflammation and regulating metabolism. However, whether scutellarin can improve IVDD remains unknown. Human primary nucleus pulposus cells (HNPCs) were cultured and stimulated with TNF-α in the presence or absence of scutellarin. Furthermore, a rat needle puncture model was established, and scutellarin was injected into the IVD to verify its protective function against IVDD. Scutellarin attenuated the inflammatory reaction and retained the production of major IVD components both in vitro and in vivo. Mechanistically, scutellarin reduced the amount of reactive oxygen species (ROS), alleviated mitochondrial damage, and decreased the expression levels of apoptosis-related biomarkers upon stimulation with TNF-α. In addition, scutellarin antagonized the activation of the nuclear factor κ-light-chain-enhancer of activated B (NF-κB) signaling pathway and the mitogen-activated protein kinase (MAPK) signaling pathway and suppressed the activity of the NLRP3 inflammasome mediated by TNF-α. This study reveals that scutellarin protects against degeneration of nucleus pulposus cells, which might shed light on treatment of IVDD in the future.

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“…The ECM surrounds the IVD cells, maintains their normal physiological functions and characteristics, and, ultimately, maintains the normal physiological structure and tissue stability of the IVD. The ECM also provides buffering capacity to resist compressive mechanical loads on the spine from all directions (Li et al, 2021). However, during the IDD process, many factors, such as aging, inflammation, oxidative stress, and abnormal pressure load, lead to imbalances in the synthesis and degradation of the ECM components in the IVD tissue, and eventually, the IVD irreversibly degenerates (Wang et al, 2020b).…”

Section: Discussionmentioning

confidence: 99%

Bardoxolone Methyl Ameliorates Compression-Induced Oxidative Stress Damage of Nucleus Pulposus Cells and Intervertebral Disc Degeneration Ex Vivo

Tian

Duan

Yang

et al. 2022

Front. Bioeng. Biotechnol.

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Intervertebral disc degeneration (IDD) is the main cause of low back pain, and little is known about its molecular and pathological mechanisms. According to reports, excessive compression is a high-risk factor for IDD; compressive stress can induce oxidative stress in nucleus pulposus (NP) cells during IDD progression that, in turn, promotes cell apoptosis and extracellular matrix (ECM) degradation. Currently, NP tissue engineering is considered a potential method for IDD treatment. However, after transplantation, NP cells may experience oxidative stress and induce apoptosis and ECM degradation due to compressive stress. Therefore, the development of strategies to protect NP cells under excessive compressive stress, including pretreatment of NP cells with antioxidants, has important clinical significance. Among the various antioxidants, bardoxolone methyl (BARD) is used to protect NP cells from damage caused by compressive stress. Our results showed that BARD can protect the viability of NP cells under compression. BARD inhibits compression-induced oxidative stress in NP cells by reducing compression-induced overproduction of reactive oxygen species (ROS) and malondialdehyde. Thus, BARD has a protective effect on the compression-induced apoptosis of NP cells. This is also supported by changes in the expression levels of proteins related to the mitochondrial apoptosis pathway. In addition, BARD can inhibit ECM catabolism and promote ECM anabolism in NP cells. Finally, the experimental results of the mechanism show that the activation of the Nrf2 signaling pathway participates in the protection induced by BARD in compressed NP cells. Therefore, to improve the viability and biological functions of NP cells under compression, BARD should be used during transplantation.

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M2a Macrophage-Secreted CHI3L1 Promotes Extracellular Matrix Metabolic Imbalances via Activation of IL-13Rα2/MAPK Pathway in Rat Intervertebral Disc Degeneration

Cited by 32 publications

References 37 publications

Reprogramming Metabolism of Macrophages as a Target for Kidney Dysfunction Treatment in Autoimmune Diseases

Reprogramming Metabolism of Macrophages as a Target for Kidney Dysfunction Treatment in Autoimmune Diseases

Scutellarin Protects Against Mitochondrial Reactive Oxygen Species-Dependent NLRP3 Inflammasome Activation to Attenuate Intervertebral Disc Degeneration

Bardoxolone Methyl Ameliorates Compression-Induced Oxidative Stress Damage of Nucleus Pulposus Cells and Intervertebral Disc Degeneration Ex Vivo

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