Serum syndecan‐4 is associated with nonalcoholic fatty liver disease

Xia, Shu Jing; Tang, Longlong; Li, Wen Hua; Xu, Zhao Shan; Zhang, Li Li; Cheng, Feng Gan; Chen, Hong Xia; Wang, Zi Hua; Luo, Yu Cheng; Dai, An Na; Fan, Jian Gao

doi:10.1111/1751-2980.13037

Cited by 7 publications

(7 citation statements)

References 45 publications

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“…Recently, syndecan-4 was also published to be a serum marker of NAFLD (7) and also acts as a receptor of HCV (57), not only infecting the hepatocytes but also responsible for the submission of the virus from men to men infecting anal Langerhans cells (58). Besides syndecan-1, syndecan-4 also regulates the Wnt signaling (59).…”

Section: Overexpression Of Spock1 Coincides With Downregulation Of Sy...mentioning

confidence: 99%

“…In the last 30 years, several publications proved the role of proteoglycans in the physiology and pathology of the liver. Although according to the literature syndecan-1 is the major heparan sulfate proteoglycan of the healthy liver, all four members of the family have been reported in increased amounts in various chronic liver diseases, such as liver fibrosis, cirrhosis (4,5), cholestasis (6), non-alcoholic fatty liver disease (NAFLD) (7), and cancer (8,9). Glypican-3 is a typical marker of hepatocellular carcinoma, detected not only in the tumor cells but also in the circulation (10).…”

Section: Introductionmentioning

confidence: 99%

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SPOCK1 Promotes the Development of Hepatocellular Carcinoma

et al. 2022

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The extracellular matrix proteoglycan SPOCK1 is increasingly recognized as a contributor to the development and progression of cancers. Here, we study how SPOCK1, which is present in non-tumorous hepatocytes at low concentrations, promotes the development and progression of malignant hepatocellular tumors. Although SPOCK1 is an extracellular matrix proteoglycan, its concentration increases in the cytoplasm of hepatocytes starting with very low expression in the normal cells and then appearing in much higher quantities in cells of cirrhotic human liver and hepatocellular carcinoma. This observation is similar to that observed after diethylnitrosamine induction of mouse hepatocarcinogenesis. Furthermore, syndecan-1, the major proteoglycan of the liver, and SPOCK1 are in inverse correlation in the course of these events. In hepatoma cell lines, the cytoplasmic SPOCK1 colocalized with mitochondrial markers, such as MitoTracker and TOMM20, a characteristic protein of the outer membrane of the mitochondrion and could be detected in the cell nucleus. SPOCK1 downregulation of hepatoma cell lines by siRNA inhibited cell proliferation, upregulated p21 and p27, and interfered with pAkt and CDK4 expression. A tyrosine kinase array revealed that inhibition of SPOCK1 in the liver cancer cells altered MAPK signaling and downregulated several members of the Sarc family, all related to the aggressivity of the hepatoma cell lines. These studies support the idea that SPOCK1 enhancement in the liver is an active contributor to human and rodent hepatocarcinogenesis and cancer progression. However, its mitochondrial localization raises the possibility that it has a currently unidentified physiological function in normal hepatocytes.

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Section: Overexpression Of Spock1 Coincides With Downregulation Of Sy...mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

SPOCK1 Promotes the Development of Hepatocellular Carcinoma

et al. 2022

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“…Importantly, univariate and multivariate analyses revealed that the age, N classification, and SDC4 expression were independent risk factors for the overall survival of PAAD patients. Existing studies highlighted the significant role of SDC4 as a potential marker for myocardial infarction [ 15 ], nonalcoholic fatty liver disease [ 16 ], and endothelial dysfunction in patients with resistant hypertension [ 17 ]. Moreover, we used GSEA and GSVA to screen the pathways associated with SDC4 enrichment, which mainly included spliceosome function, aminoacyl tRNA biosynthesis, proteasome activity, pentose phosphate pathway, base excision repair, mismatch repair, DNA replication, oxidative phosphorylation, mitotic spindle formation, epithelial-mesenchymal transition, TNFα signaling via NFKB, and G2M checkpoint.…”

Section: Discussionmentioning

confidence: 99%

High expression of syndecan-4 is related to clinicopathological features and poor prognosis of pancreatic adenocarcinoma

et al. 2022

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Objective Pancreatic adenocarcinoma (PAAD) is a leading cause of cancer-related mortality in adults. Syndecan-4 (SDC4) is involved in cancer pathogenesis. Therefore, this study aimed to explore the expression and clinical significance of SDC4 in PAAD. Methods Differentially expressed genes (DEGs) between PAAD and normal pancreas were screened from the GTEx and TCGA databases, and the correlationship between the DEGs and prognosis were analyzed. The prognostic value of the screened SDC4, SERPINE1, and SLC2A1 was evaluated using the Kaplan–Meier curve and SDC4 was subsequently selected as the better candidate. Also, SDC4 expression was analyzed in PAAD tissues, the other risk factors affecting postoperative survival were analyzed using Cox regression analysis, and SDC4-mediated pathways enrichment was identified by GSVA and GSEA. SDC4 expression in PAAD tissues and adjacent normal tissues of selected PAAD patients was detected by RT-qPCR and immunohistochemistry. The correlation between SDC4 and clinical features was evaluated by the χ2 test. Results SDC4 was highly expressed in PAAD tissues. Elevated SDC4 was correlated with reduced overall survival. SDC4 enrichment pathways included spliceosome function, proteasome activity, pentose phosphate pathway, base excision repair, mismatch repair, DNA replication, oxidative phosphorylation, mitotic spindle formation, epithelial-mesenchymal transition, and G2M checkpoints. SDC4 was elevated in PAAD tissues of PAAD patients compared with adjacent normal tissues. High SDC4 expression was related to metastatic differentiation, TNM stage, lymphatic metastasis, and lower 3-year survival rate. SDC4 was an independent risk factor affecting postoperative survival. Conclusion SDC4 was highly expressed in PAAD and was related to clinicopathological features and poor prognosis, which might be an important index for PAAD early diagnosis and prognosis.

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“…Considering that the mean and range of syndecan-4 levels in our patients overlapped with levels in healthy controls, albeit the latter in a low number, we evaluated the levels of serum syndecan-4 obtained using the same ELISA kit and sample material in published, historical controls ( Table 1 ). Although a number of studies have found significant changes in serum syndecan-4 in patient cohorts vs. healthy subjects, Table 1 demonstrates that there is a spread in the reported mean values for circulating syndecan-4 in control populations, ranging from 4.34 to 18.99 ng/mL [ 30 , 39 , 41 , 42 , 43 , 44 , 45 ]. Of note, syndecan-4 levels measured in healthy controls in one study are comparable to disease states in others.…”

Section: Discussionmentioning

confidence: 99%

Inflammation and Syndecan-4 Shedding from Cardiac Cells in Ischemic and Non-Ischemic Heart Disease

et al. 2023

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Circulating biomarkers reflecting cardiac inflammation are needed to improve the diagnostics and guide the treatment of heart failure patients. The cardiac production and shedding of the transmembrane proteoglycan syndecan-4 is upregulated by innate immunity signaling pathways. Here, we investigated the potential of syndecan-4 as a blood biomarker of cardiac inflammation. Serum syndecan-4 was measured in patients with (i) non-ischemic, non-valvular dilated cardiomyopathy (DCM), with (n = 71) or without (n = 318) chronic inflammation; (ii) acute myocarditis (n = 15), acute pericarditis (n = 3) or acute perimyocarditis (23) and (iii) acute myocardial infarction (MI) at day 0, 3 and 30 (n = 119). Syndecan-4 was investigated in cultured cardiac myocytes and fibroblasts (n = 6–12) treated with the pro-inflammatory cytokines interleukin (IL)-1β and its inhibitor IL-1 receptor antagonist (IL-1Ra), or tumor necrosis factor (TNF)α and its specific inhibitor infliximab, an antibody used in treatment of autoimmune diseases. The levels of serum syndecan-4 were comparable in all subgroups of patients with chronic or acute cardiomyopathy, independent of inflammation. Post-MI, syndecan-4 levels were increased at day 3 and 30 vs. day 0. IL-1Ra attenuated IL-1β-induced syndecan-4 production and shedding in vitro, while infliximab had no effect. In conclusion, syndecan-4 shedding from cardiac myocytes and fibroblasts was attenuated by immunomodulatory therapy. Although its circulating levels were increased post-MI, syndecan-4 did not reflect cardiac inflammatory status in patients with heart disease.

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Serum syndecan‐4 is associated with nonalcoholic fatty liver disease

Cited by 7 publications

References 45 publications

SPOCK1 Promotes the Development of Hepatocellular Carcinoma

SPOCK1 Promotes the Development of Hepatocellular Carcinoma

High expression of syndecan-4 is related to clinicopathological features and poor prognosis of pancreatic adenocarcinoma

Inflammation and Syndecan-4 Shedding from Cardiac Cells in Ischemic and Non-Ischemic Heart Disease

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