C-C Motif Chemokine Ligand-17 as a Novel Biomarker and Regulator of Epithelial Mesenchymal Transition in Renal Fibrogenesis.
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ABSTRACT:
SUBMITTER: Hsieh YH
PROVIDER: S-EPMC8699042 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundMonokines induced by interferon-gamma/Chemokine (C-X-C motif) ligand 9 (MIG/CXCL9), thymus and activation-regulated chemokine/Chemokine (C-C motif) ligand 17 (TARC/CCL17) are chemotactic factors that specifically collect and activate leukocytes, which are considered as chemoattractants of T helper cells. In the present study, we have investigated the effects of T helper type-1 (Th1) cells and T helper type-2 (Th2) cells in Kawasaki disease (KD) by determining plasma levels of MIG/CXCL9 and TARC/CCL17 and exploring the relationship between MIG/CXCL9, TARC/CCL17 levels and coronary artery lesions (CAL).MethodsForty-three children patients with KD and 19 healthy controls were included in this study. General characteristics were obtained from all subjects. Plasma concentrations of chemotactic factors of MIG/CXCL9 and TARC/CCL17 were measured by enzyme-linked immunosorbent assay (ELISA) for all subjects.ResultsPlasma levels of MIG/CXCL9, TARC/CCL17, and the ratios of MIG/TARC were significantly elevated in pediatric patients with KD compared to those in the control group. There were also significantly higher levels of MIG/CXCL9, TARC/CCL17, MIG/TARC ratios and prominently lower hemoglobin (Hb) levels in KD with CAL compared to KD without coronary artery lesions (NCAL). Hb was significantly decreased and plasma MIG/CXCL9 levels had a significantly negative correlation with CRP in KD with CAL patients (KD-CAL), whereas a positive correlation of plasma MIG/CXCL 9 with WBC was observed in KD without CAL patients (KD-NCAL).ConclusionTh1 and Th2 cells may be involved in an imbalanced activation in pediatric KD patients during an acute period of the disease. Furthermore, immune lesions of vessels in KD patients may be mediated by the imbalanced activation of Th1 and Th2 cells.
| S-EPMC4560122 | biostudies-literature
Project description:Chemokine C-X-C ligand 10 (CXCL10), also known as interferon-?-inducible protein 10 (IP-10), exerts biological function mainly through binding to its specific receptor, CXCR3. Studies have shown that renal resident mesangial cells, renal tubular epithelial cells, podocytes, endothelial cells, and infiltrating inflammatory cells express CXCL10 and CXCR3 under inflammatory conditions. In the last few years, strong experimental and clinical evidence has indicated that CXCL10 is involved in the development of renal diseases through the chemoattraction of inflammatory cells and facilitation of cell growth and angiostatic effects. In addition, CXCL10 has been shown to be a significant biomarker of disease severity, and it can be used as a prognostic indicator for a variety of renal diseases, such as renal allograft dysfunction and lupus nephritis. In this review, we summarize the structures and biological functions of CXCL10 and CXCR3, focusing on the important role of CXCL10 in the pathogenesis of kidney disease, and provide a theoretical basis for CXCL10 as a potential biomarker and therapeutic target in human kidney disease.
| S-EPMC7025113 | biostudies-literature
Project description:Barbels are important sensory organs in teleosts, reptiles, and amphibians. The majority of ?4,000 catfish species, such as the channel catfish (Ictalurus punctatus), possess abundant whisker-like barbels. However, barbel-less catfish, such as the bottlenose catfish (Ageneiosus marmoratus), do exist. Barbeled catfish and barbel-less catfish are ideal natural models for determination of the genomic basis for barbel development. In this work, we generated and annotated the genome sequences of the bottlenose catfish, conducted comparative and subtractive analyses using genome and transcriptome datasets, and identified differentially expressed genes during barbel regeneration. Here, we report that chemokine C-C motif ligand 33 (ccl33), as a key regulator of barbel development and regeneration. It is present in barbeled fish but absent in barbel-less fish. The ccl33 genes are differentially expressed during barbel regeneration in a timing concordant with the timing of barbel regeneration. Knockout of ccl33 genes in the zebrafish (Danio rerio) resulted in various phenotypes, including complete loss of barbels, reduced barbel sizes, and curly barbels, suggesting that ccl33 is a key regulator of barbel development. Expression analysis indicated that paralogs of the ccl33 gene have both shared and specific expression patterns, most notably expressed highly in various parts of the head, such as the eye, brain, and mouth areas, supporting its role for barbel development.
| S-EPMC5984497 | biostudies-literature
Project description:Allergic contact dermatitis (ACD) is a delayed-type hypersensitivity response to skin contact allergens in which keratinocytes are critical in the initiation of early responses. Keratin 17 (K17) is a cytoskeletal protein inducible under stressful conditions and regulates multiple cellular processes, especially in skin inflammatory diseases; however, knowledge regarding its contribution to ACD pathogenesis remains ill defined. In the present study, we clarified the proinflammatory role of K17 in an oxazolone (OXA)-induced contact hypersensitivity (CHS) murine model and identified the underlying molecular mechanisms. Our results showed that K17 was highly expressed in the lesional skin of ACD patients and OXA-induced CHS mice. Mice lacking K17 exhibited alleviated OXA-induced skin inflammation, including milder ear swelling, a reduced frequency of T cell infiltration, and decreased inflammatory cytokine levels. In vitro, K17 stimulated and activated human keratinocytes to produce plenty of proinflammatory mediators, especially the chemokine CCL20, and promoted keratinocyte-mediated T cell trafficking. The neutralization of CCL20 with a CCL20-neutralizing monoclonal antibody significantly alleviated OXA-induced skin inflammation in vivo. Moreover, K17 could translocate into the nucleus of activated keratinocytes through a process dependent on the nuclear-localization signal (NLS) and nuclear-export signal (NES) sequences, thus facilitating the activation and nuclear translocation of signal transducer and activator of transcription 3 (STAT3), further promoting the production of CCL20 and T cell trafficking to the lesional skin. Taken together, these results highlight the novel roles of K17 in driving allergen-induced skin inflammation and suggest targeting K17 as a potential strategy for ACD.
| S-EPMC8845002 | biostudies-literature
Project description:Background:There are few non-invasive biomarkers that have been identified to improve the risk stratification of patients with IgA nephropathy (IgAN). CXCL16 has been shown to play a key role as a chemoattractant, adhesion, and fibrosis factor in inflammatory disease. This study evaluated the potential for CXCL16 plasma as a potential biomarker in patients with IgAN. Methods:Plasma CXCL16 was measured in 230 patients with renal biopsied IgAN enrolled from 2012 to 2014. The patients were followed for 41.3 months, with a 50% reduction in estimated glomerular filtration rate or end-stage renal disease as endpoints. Results:The plasma CXCL16 levels in IgAN patients were strongly correlated with the uric acid, estimated glomerular filtration rate and tubular atrophy/interstitial fibrosis score in multivariate analysis. Furthermore, counts of CD4+ T cells, CD8+ T cells, and CD20+ B cells in renal biopsies of IgAN patients were significantly correlated with the plasma CXCL16 levels, but not CD68+ macrophage. Lastly, we concluded that patients with higher levels of plasma CXCL16 had an increased risk of poor renal outcome compared to those with lower levels. There was no association between the polymorphisms and clinical parameters of CXCL16, including the levels and prognosis of plasma CXCL16. Conclusions:Plasma CXCL16 levels were associated with clinical parameters; pathological damage; CD4+ T cell, CD8+ T cell, and CD20+ B cell infiltration in renal tissue; and renal outcome in IgAN patients. Plasma CXCL16 might be a potential prognosis predictor in Chinese IgAN patients.
| S-EPMC7186753 | biostudies-literature
Project description:Prostate-specific antigen (PSA) is regarded as the most sensitive biomarker for prostate cancer. Although androgen/androgen receptor (AR) signaling promotes prostate cancer progression, suppression of AR signaling induces chemokine (CC motif) ligand 2 (CCL2), which enables prostate cancer cells to gain metastatic potential. AR-controlled PSA alone may be an unreliable biomarker for patients receiving androgen deprivation therapy. Therefore, we investigated the validity of CCL2 as a complementary biomarker to PSA for prostate cancer. Our in vitro approach of enriching for prostate cancer cells with higher migration potential showed that CCL2 activated cellular migration. Importantly, we found that CCL2 levels were significantly different between men (n = 379) with and without prostate cancer. Patients with CCL2 ? 320 pg/mL had worse overall survival and prostate cancer -specific survival than those with CCL2 < 320 pg/mL. A novel risk classification was developed according to the risk factors CCL2 ? 320 pg/mL and PSA ? 100 ng/mL, and scores of 2, 1, and 0 were defined as poor, intermediate, and good risk, respectively, and clearly distinguished patient outcomes. CCL2 may serve as a novel biomarker for prostate cancer. The novel risk classification based on combining CCL2 and PSA is more reliable than using either alone.
| S-EPMC4885000 | biostudies-literature
Project description:The periodontal ligament (PDL) is one of the connective tissues located between the tooth and bone. It is characterized by rapid turnover. Periodontal ligament fibroblasts (PDLFs) play major roles in the rapid turnover of the PDL. Microarray analysis of human PDLFs (HPDLFs) and human dermal fibroblasts (HDFs) revealed markedly high expression of chemokine (CXC motif) ligand 12 (CXCL12) in the HPDLFs, which plays an important role in the migration of mesenchymal stem cells (MSCs). The function of CXCL12 in the periodontal ligament was investigated in HPDLFs. CXCL12 in HPDLFs and HDFs was examined by microarray, RT-PCR, qRT-PCR and ELISA. It was also immunohistochemically examined in the PDL in vivo. Chemotactic ability of CXCL12 was evaluated both in PDLFs and HDFs with migration assay of MSCs. The expression of CXCL12 in the HPDLFs was much higher than that in HDFs in vitro. CXCL12 was localized in fibroblasts and extracellular matrix in the PDL in rats. Migration assay demonstrated that the number of migrated MSCs by HPDLFs was significantly higher than that by HDFs. In addition, the migrated MSCs also expressed CXCL12 and several genes that are familiar to fibroblasts. The results suggested that PDLFs are able to synthesize and secrete CXCL12 protein, and that CXCL12 induces migration of MSCs in the PDL in order to maintain rapid turnover of the PDL. The objective of this study was to investigate the function of CXCL12 in the PDL with rapid turnover.Microarray analysis was performed using a Whole Human Genome 8x60K (Agilent Technologies, Tokyo, Japan) containing approximately 44,000 transcripts. According to the manufacturerM-bM-^@M-^Ys protocol, total RNAs from HPDLFs and HDFs were labeled with Cy3 and hybridized on the microarray. The hybridization data for HPDLFs were compared with data for HDFs.
2013-11-07 | E-GEOD-52162 | biostudies-arrayexpress
Project description:Background and purposeInflammatory mediators in blood have been proposed as potential biomarkers in stroke. However, a direct relationship between these circulating factors and brain-specific ischemic injury remains to be fully defined.MethodsAn unbiased screen in a nonhuman primate model of stroke was used to find out the most responsive circulating biomarker flowing ischemic stroke. Then this phenomenon was checked in human beings and mice. Finally, we observed the temporospatial responsive characteristics of this biomarker after ischemic brain injury in mice to evaluate the direct relationship between this circulating factor and central nervous system–specific ischemic injury.ResultsIn a nonhuman primate model, an unbiased screen revealed CCL2 (C-C motif chemokine ligand 2) as a major response factor in plasma after stroke. In mouse models of focal cerebral ischemia, plasma levels of CCL2 showed a transient response, that is, rapidly elevated by 2 to 3 hours postischemia but then renormalized back to baseline levels by 24 hours. However, a different CCL2 temporal profile was observed in whole brain homogenate, cerebrospinal fluid, and isolated brain microvessels, with a progressive increase over 24 hours, demonstrating a mismatch between brain versus plasma responses. In contrast to the lack of correlation with central nervous system responses, 2 peripheral compartments showed transient profiles that matched circulating plasma signatures. CCL2 protein in lymph nodes and adipose tissue was significantly increased at 2 hours and renormalized by 24 hours.ConclusionsThese findings may provide a cautionary tale for biomarker pursuits in plasma. Besides a direct central nervous system response, peripheral organs may also contribute to blood signatures in complex and indirect ways.
| S-EPMC8545911 | biostudies-literature
Project description:The periodontal ligament (PDL) is one of the connective tissues located between the tooth and bone. It is characterized by rapid turnover. Periodontal ligament fibroblasts (PDLFs) play major roles in the rapid turnover of the PDL. Microarray analysis of human PDLFs (HPDLFs) and human dermal fibroblasts (HDFs) revealed markedly high expression of chemokine (CXC motif) ligand 12 (CXCL12) in the HPDLFs, which plays an important role in the migration of mesenchymal stem cells (MSCs). The function of CXCL12 in the periodontal ligament was investigated in HPDLFs. CXCL12 in HPDLFs and HDFs was examined by microarray, RT-PCR, qRT-PCR and ELISA. It was also immunohistochemically examined in the PDL in vivo. Chemotactic ability of CXCL12 was evaluated both in PDLFs and HDFs with migration assay of MSCs. The expression of CXCL12 in the HPDLFs was much higher than that in HDFs in vitro. CXCL12 was localized in fibroblasts and extracellular matrix in the PDL in rats. Migration assay demonstrated that the number of migrated MSCs by HPDLFs was significantly higher than that by HDFs. In addition, the migrated MSCs also expressed CXCL12 and several genes that are familiar to fibroblasts. The results suggested that PDLFs are able to synthesize and secrete CXCL12 protein, and that CXCL12 induces migration of MSCs in the PDL in order to maintain rapid turnover of the PDL.
2013-11-07 | GSE52162 | GEO
Project description:We examined interrelationships between chemokine C-C motif ligand 2 (CCL2) genotype and expression of inflammatory markers in the cerebrospinal fluid (CSF), plasma viral load, CD4 cell count and neurocognitive functioning among HIV-infected adults. We hypothesized that HIV-positive carriers of the 'risk' CCL2 -2578G allele, caused by a single nucleotide polymorphism (SNP) at rs1024611, would have a higher concentration of CCL2 in CSF, and that CSF CCL2 would be associated with both higher concentrations of other proinflammatory markers in CSF and worse neurocognitive functioning.A cross-sectional study of 145 HIV-infected individuals enrolled in the National NeuroAIDS Tissue Consortium cohort for whom genotyping, CSF and neurocognitive data were available.Genomic DNA was extracted from peripheral blood mononuclear cells and/or frozen tissue specimens. CSF levels of CCL2, interleukin (IL)-2, IL-6, tumour necrosis factor-alpha (TNF-?), interferon-gamma (IFN-?), soluble tumor necrosis factor receptor 2, sIL-6R?, sIL-2, sCD14 and B-cell activating factor were quantified. Neurocognitive functioning was measured using a comprehensive battery of neuropsychological tests.Carriers of the CCL2 -2578G allele had a significantly higher concentration of CCL2 in CSF. CSF CCL2 level was positively and significantly associated with other CSF neuroinflammatory markers and worse cognitive functioning. There was a significant association between genotype and plasma viral load, such that carriers of the CCL2 -2578G allele with high viral load expressed greater levels of CCL2 and had higher neurocognitive deficit scores than other genotype/viral load groups.Individuals with the CCL2 -2578G allele had higher levels of CCL2 in CSF, which was associated with increased pro-inflammatory markers in CSF and worse neurocognitive functioning. The results highlight the potential role of intermediate phenotypes in studies of genotype and cognition.
| S-EPMC4573552 | biostudies-literature