Selective suppression of M1 macrophages is involved in zinc inhibition of liver fibrosis in mice

Xie, Chengxia; Wan, Lin; Li, Chen; Feng, Yinrui; Kang, Yup

doi:10.1016/j.jnutbio.2021.108802

Cited by 10 publications

(4 citation statements)

References 46 publications

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“…Macrophages can undergo classically activated M1 polarization (pro-inflammatory) or alternatively activated M2 polarization (anti-inflammatory) in response to microenvironment cues. Recent studies suggest that macrophages switched to the M1 phenotype exert pro-inflammatory as well as pro-fibrogenic roles in the pathogenesis of liver fibrosis [ 46 , 47 , 48 ], while macrophages polarized to M2 phenotype responding to the stimulation of IL-4 or IL-13 attenuate the progression of liver fibrosis [ 49 , 50 ]. Hence, M1/M2 macrophage polarization provides an insight into the mechanisms regulating the resolution or progression of liver fibrosis.…”

Section: Discussionmentioning

confidence: 99%

Sappanone A Alleviates the Severity of Carbon Tetrachloride-Induced Liver Fibrosis in Mice

Qi,

Li,

Yan

et al. 2023

Antioxidants

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Liver fibrosis is a major challenge to global health because of its various complications, including cirrhosis and hepatocarcinoma, while no effective treatment is available for it. Sappanone A (SA) is a homoisoflavonoid extracted from the heartwood of Caesalpinia sappan Linn. with anti-inflammatory and antioxidant properties. However, the effects of SA on hepatic fibrosis remain unknown. This study aimed to investigate the protective effects of SA on carbon tetrachloride (CCl4)-induced liver fibrosis in mice. To establish a liver fibrosis model, mice were treated intraperitoneally (i.p.) with CCl4 for 4 weeks. SA (25, 50, and 100 mg/kg body weight) was i.p. injected every other day during the same period. Our data indicated that SA decreased liver injury, fibrotic responses, and inflammation due to CCl4 exposure. Consistently, SA reduced oxidative stress and its-mediated hepatocyte death in fibrotic livers. Of note, SA could not directly affect the activation of hepatic stellate cells. Mechanistically, SA treatment lessened oxidative stress-triggered cell death in hepatocytes after CCl4 exposure. SA down-regulated the expression of M1 macrophage polarization markers (CD86 and iNOS) and up-regulated the expression of M2 macrophage polarization markers (CD163, IL-10, and Arg1) in livers and macrophages. Meanwhile, SA induced the activation of peroxisome proliferator-activated receptor gamma (PPARγ). However, decreased inflammatory responses and the trend of M2 macrophage polarization provided by SA were substantially abolished by SR202 (a PPARγ inhibitor) treatment in macrophages. Additionally, SA treatment promoted fibrosis regression. Taken together, our findings revealed that treatment with SA alleviated CCl4-induced fibrotic liver in mice through suppression of oxidative stress-mediated hepatocyte death and promotion of M2 macrophage polarization via PPARγ. Thus, SA might pave the way for a new hepatoprotective agent to treat liver fibrosis.

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Section: Discussionmentioning

confidence: 99%

Sappanone A Alleviates the Severity of Carbon Tetrachloride-Induced Liver Fibrosis in Mice

Qi,

Li,

Yan

et al. 2023

Antioxidants

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“…The sections were stained with hematoxylin–eosin (HE), periodic acid‐Schiff (PAS), and Masson for light microscopic analysis and pathological observation. As described in our previous study, 27 the paraffin sections were performed in immunohistochemistry (IHC). Briefly, the sections were stained gradually with primary antibody against MAGI2 (Thermo Scientific, USA), a peroxidase‐conjugated secondary antibody, and DAB staining.…”

Section: Methodsmentioning

confidence: 99%

MAGI2 ameliorates podocyte apoptosis of diabetic kidney disease through communication with TGF‐β‐Smad3/nephrin pathway

Wang,

Li,

Wang

et al. 2023

The FASEB Journal

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Podocytes, the key component of the glomerular filtration barrier (GFB), are gradually lost during the progression of diabetic kidney disease (DKD), severely compromising kidney functionality. The molecular mechanisms regulating the survival of podocytes in DKD are incompletely understood. Here, we show that membrane‐associated guanylate kinase inverted 2 (MAGI2) is specifically expressed in renal podocytes, and promotes podocyte survival in DKD. We found that MAGI2 expression was downregulated in podocytes cultured with high‐glucose in vitro, and in kidneys of db/db mice as well as DKD patients. Conversely, we found enforced expression of MAGI2 via AAV transduction protected podocytes from apoptosis, with concomitant improvement of renal functions. Mechanistically, we found that MAGI2 deficiency induced by high glucose levels activates TGF‐β signaling to decrease the expression of anti‐apoptotic proteins. These results indicate that MAGI2 protects podocytes from cell death, and can be harnessed therapeutically to improve renal function in diabetic kidney disease.

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“…The fibrotic process in CKD involves a complex interaction involving inflammation, RAAS, PTH, FGF23/klotho axis, microRNAs and vitamin D [194]. Some studies have highlighted the antifibrotic properties of zinc in the liver and lungs [196][197][198], and it is promising in reducing the risk of fibrosis progression even in patients with chronic renal failure. Current findings indicate that supplementation improves nutritional health and mitigates oxidative stress among individuals with zinc deficiency.…”

Section: Zinc (Zn)mentioning

confidence: 99%

Role of Nutrients in Pediatric Non-Dialysis Chronic Kidney Disease: From Pathogenesis to Correct Supplementation

Padoan,

Guarnaroli,

Brugnara

et al. 2024

Biomedicines

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Nutrition management is fundamental for children with chronic kidney disease (CKD). Fluid balance and low-protein and low-sodium diets are the more stressed fields from a nutritional point of view. At the same time, the role of micronutrients is often underestimated. Starting from the causes that could lead to potential micronutrient deficiencies in these patients, this review considers all micronutrients that could be administered in CKD to improve the prognosis of this disease.

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Selective suppression of M1 macrophages is involved in zinc inhibition of liver fibrosis in mice

Cited by 10 publications

References 46 publications

Sappanone A Alleviates the Severity of Carbon Tetrachloride-Induced Liver Fibrosis in Mice

Sappanone A Alleviates the Severity of Carbon Tetrachloride-Induced Liver Fibrosis in Mice

MAGI2 ameliorates podocyte apoptosis of diabetic kidney disease through communication with TGF‐β‐Smad3/nephrin pathway

Role of Nutrients in Pediatric Non-Dialysis Chronic Kidney Disease: From Pathogenesis to Correct Supplementation

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