Functional Roles of Chemokine Receptor CCR2 and Its Ligands in Liver Disease

She, Shaoping; Ren, Liying; Chen, Pu; Wang, Mingyang; Chen, Dongbo; Wang, Ying; Chen, Hongsong

doi:10.3389/fimmu.2022.812431

Cited by 58 publications

(46 citation statements)

References 153 publications

(243 reference statements)

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“…Experiments in mice indicate that the development of cirrhosis can actually be delayed by CCL16 via the inhibition of hepatic stellate cells, suggesting that this chemokine may exert a unique disease-limiting role in the liver [ 69 ]. Notably, a recent evaluation of a large number of HCC samples confirmed that mean CCL16 mRNA levels were essentially unchanged with respect to non-tumour tissue, but also revealed a low-populated tail of the distribution extending towards very high figures, which was not observed in the reference group [ 70 ]. These samples may reflect cases with more significant local inflammation, possibly leading to CCL16 induction in non-hepatocytes, or with overproduction by the tumour cells themselves; our HBV-related tumour cohort featuring a lower number of specimens with a single outlier ( Figure 2 ) may actually be sampling the same underlying distribution.…”

Section: Resultsmentioning

confidence: 99%

Structure and Dynamics of Human Chemokine CCL16—Implications for Biological Activity

et al. 2022

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Human C-C motif ligand 16 (CCL16) is a chemokine that is distinguished by a large cleavable C-terminal extension of unknown significance. Conflicting data have been reported concerning its tissue distribution and modulation of expression, rendering the biological function of CCL16 enigmatic. Here, we report an integrated approach to the characterisation of this chemokine, including a re-assessment of its expression characteristics as well as a biophysical investigation with respect to its structure and dynamics. Our data indicate that CCL16 is chiefly synthesised by hepatocytes, without an appreciable response to mediators of inflammation, and circulates in the blood as a full-length protein. While the crystal structure of CCL16 confirms the presence of a canonical chemokine domain, molecular dynamics simulations support the view that the C-terminal extension impairs the accessibility of the glycosaminoglycan binding sites and may thus serve as an intrinsic modulator of biological activity.

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Section: Resultsmentioning

confidence: 99%

Structure and Dynamics of Human Chemokine CCL16—Implications for Biological Activity

et al. 2022

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“…CCR2 regulated the migration and positioning of immune cells within tissues were critical for the function of the immune system. CCR2 participated in liver pathology, including acute liver injury (ALI), chronic hepatitis, brosis/cirrhosis, and tumor progression, by mediating the recruitment of immune cells to in ammation and tumor sites [17]. CCR2 de ciency reduced brosis and CCR2 was required for recruitment of hepatic macrophages [18].…”

Section: Discussionmentioning

confidence: 99%

Unveiling the Hub Genes Associated with Manganese-Induced Hepatotoxicity

Yang

Wang

et al. 2023

Preprint

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Excessive exposure to manganese (Mn) can cause severe toxicity in human and animal organs, particularly the liver. However, the specific mechanisms of Mn-induced hepatotoxicity remain unclear. Thus, the objective of this study was to identify the key genes associated with hepatotoxicity caused by Mn administration. We obtained the gene expression data set GSE59923 from the Gene Expression Omnibus, which included liver samples treated with manganese chloride (MnCl2) as well as control samples. Through our analysis, we identified 222, 351, and 494 differentially expressed genes (DEGs) in the livers treated with MnCl2 at 700 mg/kg on the 1st, 3rd, and 5th day, respectively. Notably, we found a total of 27 overlapping DEGs in the liver samples. Biological process analysis revealed that these common DEGs were associated with the response to xenobiotic stimulus, cellular calcium ion homeostasis, and ion transmembrane transport. Pathway analysis further indicated the involvement of cAMP, p53, PI3K-Akt, MAPK, and AMPK signaling pathways in Mn-induced hepatotoxicity. Furthermore, we identified several important genes, including CCR2, CDKN1A, CELSR2, LCN2, and PER2, which appeared to play a role in Mn-induced hepatotoxicity. Taken together, this study sheds light on the molecular mechanisms underlying Mn-induced hepatotoxicity, contributing to our overall understanding of this condition.

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“…CCL13, or monocyte chemoattract protein-4 (MCP-4), is a molecule that induces chemotaxis in monocytes⁄macrophages, T lymphocytes, and eosinophils by binding cell surface chemokine receptors such as CCR2, CCR3, and CCR5 [ 170 ]. It also plays an important role in different cell functions, including migration, invasion, motility, and proliferation [ 170 ]. Two different studies measured circulating CCL13 levels in SSc patients [ 171 , 172 ].…”

Section: Cytokinesmentioning

confidence: 99%

Current Trends in Vascular Biomarkers for Systemic Sclerosis: A Narrative Review

Fioretto

Rosa

Matucci‐Cerinic

et al. 2023

IJMS

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Systemic sclerosis (SSc, scleroderma) is a multifaceted rare connective tissue disease whose pathogenesis is dominated by immune dysregulation, small vessel vasculopathy, impaired angiogenesis, and both cutaneous and visceral fibrosis. Microvascular impairment represents the initial event of the disease, preceding fibrosis by months or years and accounting for the main disabling and/or life-threatening clinical manifestations, including telangiectasias, pitting scars, periungual microvascular abnormalities (e.g., giant capillaries, hemorrhages, avascular areas, ramified/bushy capillaries) clinically detectable by nailfold videocapillaroscopy, ischemic digital ulcers, pulmonary arterial hypertension, and scleroderma renal crisis. Despite a variety of available treatment options, treatment of SSc-related vascular disease remains problematic, even considering SSc etherogenity and the quite narrow therapeutic window. In this context, plenty of studies have highlighted the great usefulness in clinical practice of vascular biomarkers allowing clinicians to assess the evolution of the pathological process affecting the vessels, as well as to predict the prognosis and the response to therapy. The current narrative review provides an up-to-date overview of the main candidate vascular biomarkers that have been proposed for SSc, focusing on their main reported associations with characteristic clinical vascular features of the disease.

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Functional Roles of Chemokine Receptor CCR2 and Its Ligands in Liver Disease

Cited by 58 publications

References 153 publications

Structure and Dynamics of Human Chemokine CCL16—Implications for Biological Activity

Structure and Dynamics of Human Chemokine CCL16—Implications for Biological Activity

Unveiling the Hub Genes Associated with Manganese-Induced Hepatotoxicity

Current Trends in Vascular Biomarkers for Systemic Sclerosis: A Narrative Review

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