Knockdown of ANGPTL-4 inhibits inflammatory response and extracellular matrix accumulation in glomerular mesangial cells cultured under high glucose condition

Qin, Linfang; Zhang, Ruimin; Yang, Suxia; Chen, Fang; Shi, Jun

doi:10.1080/21691401.2019.1649274

Cited by 21 publications

(9 citation statements)

References 23 publications

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“…ANGPTL4 was also involved in inflammation, and the production of pro-inflammatory cytokines including TNF-α, IL-1β, and IL-6 were decreased in ANGPTL4 knocked down mesangial cells. Inhibition of ANGPTL4 markedly suppressed the expression of extracellular matrix (ECM) proteins, collagen IV, and fibronectin, in high glucose-stimulated mesangial cells [31]. Previous studies found a positive association between ANGPTL8 expression and degenerative grades of intervertebral disc degeneration.…”

Section: Discussionmentioning

confidence: 92%

Increased Circulating Angiopoietin-Like Protein 8 Levels Are Associated with Thoracic Aortic Dissection and Higher Inflammatory Conditions

Yang

Jiao

et al. 2020

Cardiovasc Drugs Ther

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Purpose Thoracic aortic dissection (TAD) is characterized by an inflammatory response. Angiopoietin-like protein 8 (ANGPTL8) is a hormone involved in the regulation of lipid metabolism and inflammation. However, the relationship between ANGPTL8 and TAD remains unknown. Methods This case-control study included 78 TAD patients and 72 controls. The aortic diameter was evaluated by computed tomography and used to assess TAD severity. Circulating ANGPTL8 levels were measured by enzyme-linked immunosorbent assay. Associations of ANGPTL8 with TAD were determined by multivariate logistic regression. Results Serum ANGPTL8 levels were significantly higher in TAD patients compared with controls (562.50 ± 20.84 vs. 419.70 ± 22.65 pg/mL, respectively; P < 0.001). After adjusting for confounding factors, circulating ANGPTL8 levels were an independent risk factor for TAD (odds ratio = 1.587/100 pg ANGPTL8, 95% confidence interval [CI] = 1.121–2.247, P < 0.001) and positively associated with diameter (β = 1.081/100 pg ANGPTL8, 95% CI = 0.075–2.086, P = 0.035) and high-sensitivity C-reactive protein (hs-CRP) (β = 0.845/100 pg ANGPTL8, 95% CI = 0.020–1.480, P = 0.009). The area under the curve (AUC) on receiver operating characteristic (ROC) analysis of the combination of ANGPTL8, hs-CRP, and D-dimer was 0.927, and the specificity and sensitivity were 98.46% and 79.49%, respectively. ANGPTL8 was significantly increased in TAD tissue compared with controls. In vitro, ANGPTL8 was increased in angiotensin II (AngII)-treated macrophages and vascular smooth muscle cells (VSMCs), while ANGPTL8 siRNA-mediated knockdown decreased inflammatory factors in AngII-treated macrophages and decreased apoptosis in AngII-treated VSMCs. Conclusion ANGPTL8 is associated with TAD occurrence and development, which may involve pro-inflammatory effects on macrophages. ANGPTL8 combined with D-dimer and hs-CRP might be a useful clinical predictor of TAD. Trial Registration ChiCTR-COC-17010792 http://www.chictr.org.cn/showproj.aspx?proj=18288

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Section: Discussionmentioning

confidence: 92%

Increased Circulating Angiopoietin-Like Protein 8 Levels Are Associated with Thoracic Aortic Dissection and Higher Inflammatory Conditions

Yang

Jiao

et al. 2020

Cardiovasc Drugs Ther

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“…It was shown that ANGPTL-4 expression was positively correlated with the amount of 24-h urine protein, sCr and the kidney weight index ( 41 ). It was also demonstrated that ANGPTL-4 was over-expressed in DN rat and associated with HG-induced cell proliferation, inflammatory response, and extracellular matrix accumulation in glomerular mesangial cells, mediating damage to the glomerular filtration barrier ( 41 , 42 ). Besides, syndecan-1 shedding may also play a role in the development of DN ( 40 ).…”

Section: Discussionmentioning

confidence: 99%

Correlations Between Different Angiogenic and Inflammatory Factors in Vitreous Fluid of Eyes With Proliferative Diabetic Retinopathy

Tang

et al. 2021

Front. Med.

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Purpose: To investigate the expression of various angiogenesis and inflammation mediators in the vitreous fluid of eyes with proliferative diabetic retinopathy (PDR).Methods: A total of 38 eyes with PDR and 37 control eyes were included. Vitreous fluid was collected during vitrectomy. Vitreous levels of colony stimulating factor-1 receptor (CSF-1R), syndecan-1, placental growth factor (PIGF), and angiopoietin-like protein 4 (ANGPTL-4) were measured by multiplex immunoassay. Vitreous levels of vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), interleukin-8 (IL-8), monocyte chemotactic protein-1 (MCP-1), tumor necrosis factor-α (TNF-α), and intercellular adhesion molecule-1 (ICAM-1) were measured by cytometric beads array. Levels of these mediators were compared between the PDR and control eyes. Correlations between levels of different mediators and between these mediators and kidney function metrics in the PDR group were also analyzed.Results: Vitreous levels of syndecan-1, PIGF, ANGPTL-4, VEGF, and IL-8 were significantly higher in the PDR group compared to the control group (all p < 0.05). Levels of VEGF were significantly correlated with levels of syndecan-1, PIGF, and ANGPTL-4 (r = 0.370 to 0.497, all p < 0.05). Significant positive correlations were detected between levels of any two of the following mediators including syndecan-1, PIGF, ANGPTL-4, and IL-8 (r = 0.370 to 0.906, all p < 0.05). Apart from VEGF, levels of these mediators were positively correlated with serum creatinine and blood urea nitrogen (r = 0.328 to 0.638, all p < 0.05), and negatively correlated with fasting blood glucose and estimated glomerular filtration rate (r = −0.325 to −0.603, all p < 0.05).Conclusions: Correlations between different angiogenesis and inflammation mediators were observed in eyes with PDR, suggesting cross-talks of different angiogenesis and inflammation pathways in the pathogenesis of PDR. The levels of angiogenesis and inflammation in PDR are correlated with kidney damage, indicating possible common pathways in diabetic retinopathy and nephropathy.

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“…Regarding the nephrotoxicity biomarker gene panel, Angptl4 kidney expression was found to be upregulated in tapentadol-treated rats ( Figure 6 b). Angptl4, angiopoietin-like 4 protein, is secreted from podocytes, having been implicated in processes as diverse as glucose and energy homeostasis, angiogenesis and vascular permeability, inflammation, tumorigenesis, cell differentiation, wound healing and redox regulation [ 202 , 203 , 204 ]. It induces morphological and clinical manifestations of human minimal change disease and is being increasingly recognized as a contributor to proteinuria in experimental diabetic nephropathy [ 152 , 172 , 173 , 205 ].…”

Section: Discussionmentioning

confidence: 99%

Repeated Administration of Clinical Doses of Tramadol and Tapentadol Causes Hepato- and Nephrotoxic Effects in Wistar Rats

et al. 2020

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Tramadol and tapentadol are fully synthetic and extensively used analgesic opioids, presenting enhanced therapeutic and safety profiles as compared with their peers. However, reports of adverse reactions, intoxications and fatalities have been increasing. Information regarding the molecular, biochemical, and histological alterations underlying their toxicological potential is missing, particularly for tapentadol, owing to its more recent market authorization. Considering the paramount importance of liver and kidney for the metabolism and excretion of both opioids, these organs are especially susceptible to toxicological damage. In the present study, we aimed to characterize the putative hepatic and renal deleterious effects of repeated exposure to therapeutic doses of tramadol and tapentadol, using an in vivo animal model. Male Wistar rats were randomly divided into six experimental groups, composed of six animals each, which received daily single intraperitoneal injections of 10, 25 or 50 mg/kg tramadol or tapentadol (a low, standard analgesic dose, an intermediate dose and the maximum recommended daily dose, respectively). An additional control group was injected with normal saline. Following 14 consecutive days of administration, serum, urine and liver and kidney tissue samples were processed for biochemical, metabolic and histological analysis. Repeated administration of therapeutic doses of both opioids led to: (i) increased lipid and protein oxidation in liver and kidney, as well as to decreased total liver antioxidant capacity; (ii) decreased serum albumin, urea, butyrylcholinesterase and complement C3 and C4 levels, denoting liver synthesis impairment; (iii) elevated serum activity of liver enzymes, such as alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and γ-glutamyl transpeptidase, as well as lipid profile alterations, also reflecting hepatobiliary commitment; (iv) derangement of iron metabolism, as shown through increases in serum iron, ferritin, haptoglobin and heme oxygenase-1 levels. In turn, elevated serum cystatin C, decreased urine creatinine output and increased urine microalbumin levels were detected upon exposure to tapentadol only, while increased serum amylase and urine N-acetyl-β-D-glucosaminidase activities were observed for both opioids. Collectively, these results are compatible with kidney injury. Changes were also found in the expression levels of liver- and kidney-specific toxicity biomarker genes, upon exposure to tramadol and tapentadol, correlating well with alterations in lipid profile, iron metabolism and glomerular and tubular function. Histopathological analysis evidenced sinusoidal dilatation, microsteatosis, mononuclear cell infiltrates, glomerular and tubular disorganization, and increased Bowman’s spaces. Although some findings are more pronounced upon tapentadol exposure, our study shows that, when compared with acute exposure, prolonged administration of both opioids smooths the differences between their toxicological effects, and that these occur at lower doses within the therapeutic range.

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Knockdown of ANGPTL-4 inhibits inflammatory response and extracellular matrix accumulation in glomerular mesangial cells cultured under high glucose condition

Cited by 21 publications

References 23 publications

Increased Circulating Angiopoietin-Like Protein 8 Levels Are Associated with Thoracic Aortic Dissection and Higher Inflammatory Conditions

Increased Circulating Angiopoietin-Like Protein 8 Levels Are Associated with Thoracic Aortic Dissection and Higher Inflammatory Conditions

Correlations Between Different Angiogenic and Inflammatory Factors in Vitreous Fluid of Eyes With Proliferative Diabetic Retinopathy

Repeated Administration of Clinical Doses of Tramadol and Tapentadol Causes Hepato- and Nephrotoxic Effects in Wistar Rats

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