Chemokine Ligand 13 Expression is Abundant in the Tumor Microenvironment and Indicates Poor Prognosis of Kidney Clear Cell Carcinoma

Wu, Mengdan; Sun, Mengyao; Lai, Qinhuai; Lu, Yin; Fu, Yang; Peng, Yujia; Lai, Weirong; Zeng, Lei; Zhao, Shengyan; Li, Yuyan; Zhang, Zhixiong; Chen, Xiaofeng; Qiao, Fan; Zhang, Yiwen; Zhou, Shijie; Gou, Lantu; Yang, Jinliang

doi:10.32604/biocell.2021.013882

Cited by 5 publications

(3 citation statements)

References 33 publications

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“…TLR4 is the first identified TLR that recognizes lipopolysaccharides (LPS) of Gram-negative bacteria and activates inflammation via MAL-myeloid differentiation factor 88 (MyD88) dependent and independent signaling pathways [ 11 ]. TLR4 signaling has been shown to contribute to intestine inflammation [ 12 ]. However, the link between TLR4 and ER stress in the development of IBD and the underlying signaling pathways are unclear.…”

Section: Introductionmentioning

confidence: 99%

TLR4 promoted endoplasmic reticulum stress induced inflammatory bowel disease via the activation of p38 MAPK pathway

Zhao

Long

et al. 2022

Bioscience Reports

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Endoplasmic reticulum (ER) stress contribute to inflammatory bowel disease (IBD). However, the mechanistic link between TLR4 and ER stress in IBD remains elusive. This study aimed to investigate the mechanism by whichERstress and TLR4 promote inflammation in IBD. IBD mouse model was established by the induction of TNBS, and Grp78 and TLR4 in intestine tissues were detected by immunohistochemistry. THP-1 cells were treated with LPS, ER stress inducer or inhibitor TUDCA, or p38 MAPK inhibitor. The activation of MAPK signaling was detected by Western blot, and the production and secretion of inflammatory factors were detected by PCR and ELISA. We found that the expression levels of TLR4 and GRP78 were significantly higher in the intestine of IBD model mice compared to control mice, but were significantly lower in the intestine of IBD model mice treated with ER stress inhibitor TUDCA. ER stress inducer significantly increased while ER stress inhibitor TUDCA significantly decreased the expression and secretion of TNF-α, IL-1β and IL-8 in THP-1 cells treated by LPS. Only p38 MAPK signaling was activated in THP-1 cells treated by ER stress inducer. Furthermore, p38 inhibitor SB203580 inhibited the production and secretion of TNF-α, IL-1β and IL-8 in THP-1 cells treated with LPS. In conclusion, TLR4 promotes ER stress induced inflammation in IBD, and the effects may be mediated by p38 MAPK signaling. TLR4 and p38 MAPK signaling are novel therapeutic targets for IBD.

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Section: Introductionmentioning

confidence: 99%

TLR4 promoted endoplasmic reticulum stress induced inflammatory bowel disease via the activation of p38 MAPK pathway

Zhao

Long

et al. 2022

Bioscience Reports

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“…Tumorigenesis typically involves complex interactions with surrounding environmental factors, and different environments suggest different directions of differentiation and evolution 28 . Tumor heterogeneity refers to the phenomenon that tumor cells interact with influential factors in the tumor microenvironment, with different evolutionary directions in temporal and spatial dimensions 12 .…”

Section: Discussionmentioning

confidence: 99%

Single-cell analysis reveals ADGRL4+ renal tubule cells as a highly aggressive cell type in clear cell renal cell carcinoma

Wang,

Zhang

2024

Sci Rep

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Clear cell renal cell carcinoma (ccRCC) is a highly heterogeneous cancer that poses great challenge to clinical treatment and prognostic prediction. Characterizing the cellular landscape of ccRCC in a single-cell dimension can help better understand the tumor heterogeneity and molecular mechanisms of ccRCC. This study analyzed single-cell profiles in ccRCC samples and para-tumor samples from Gene Expression Omnibus and identified a highly heterogeneous subcluster of renal tubule cells. Single-cell regulatory network inference and clustering analyses and cell communication analysis were performed to develop transcription factor-target gene regulatory networks and cell–cell interactions. Additionally, the distribution and prognostic risk of renal tubule cells from spatial transcriptome data (GSM6415706) and The Cancer Genome Atlas-Kidney Clear Cell Carcinoma data were analyzed. A total of 10 cell types were identified in ccRCC and para-tumor samples. The ccRCC renal tubule cells showed a high expression of the oncogene nicotinamide N-methyltransferase and a significantly high degree of tumor heterogeneity. We further identified 6 cell subclusters with specific expression of BEX2, PTHLH, SFRP2, KLRB1, ADGRL4, and HGF from the ccRCC renal tubule cells. ADGRL4+ renal tubule cells had highly metastatic and angiogenesis-inducing characteristics, with more ADGRL4+ renal tubule cells indicating a worse survival. ADGRL4+ renal tubule cells regulated the metastasis of other renal tubule cells through metastasis-related receptor-ligand communication. We also found that ADGRL4+ renal tubule cells clustered around the glomeruli but the rest of the renal tubule cell subclusters rarely localized in ccRCC tissues. ETS1 and ELK3 -dominant GRNs were remarkably activated in ADGRL4+ renal tubule cells, functionally, knockdown of ELK3 in A498 significantly disturbedaffected the cell migration and invasion. ADGRL4+ renal tubule cells, which were highly metastatic and invasive, might be an essential cell subcluster for ccRCC, and ADGRL4 could be used a novel therapeutic target.

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“…In particular, interleukin 8 (IL-8) and its receptor are upregulated in intestinal mucosa. 9-12 IL-8 is one of the members of the CXC chemokine family which recruits neutrophil to inflamed sites. Previous studies have confirmed that IL-8 was expressed in the intestinal mucosa of IBD, and IL-8 expression level was correlated with disease activity.…”

Section: Introductionmentioning

confidence: 99%

Endoplasmic reticulum stress contributed to inflammatory bowel disease by activating p38 MAPK pathway

Long

Zhao

et al. 2022

Eur J Histochem

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Recent evidence suggests that endoplasmic reticulum (ER) stress plays a vital role in inflammatory bowel disease (IBD). Therefore, the aim of this study was to investigate the mechanism by which ER stress promotes inflammatory response in IBD. The expression of Gro-α, IL-8 and ER stress indicator Grp78 in colon tissues from patients with Crohn’s disease (CD) and colonic carcinoma was analyzed by immunohistochemistry staining. Colitis mouse model was established by the induction of trinitrobenzene sulphonic acid (TNBS), and the mice were treated with ER stress inhibitor tauroursodeoxycholic acid (TUDCA). Then the body weight, colon length and colon inflammation were evaluated, and Grp78 and Gro-α in colon tissues were detected by immunohistochemistry. Epithelial cells of colon cancer HCT116 cells were treated with tunicamycin to induce ER stress. Grp78 was detected by Western blot, and chemokines were measured by PCR and ELISA. The expression levels of Grp78, Gro-α and IL-8 were significantly upregulated in intestinal tissues of CD patients. Mice with TNBS induced colitis had increased expression of Grp78 and Gro-α in colonic epithelia. TUDCA reduced the severity of TNBS-induced colitis. In HCT116 cells, tunicamycin increased the expression of Grp78, Gro-α and IL-8 in a concentration-dependent manner. Furthermore, p38 MAPK inhibitor significantly inhibited the upregulation of Gro-α and IL-8 induced by tunicamycin. In conclusion, ER stress promotes inflammatory response in IBD, and the effects may be mediated by the activation of p38 MAPK signaling pathway.

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Chemokine Ligand 13 Expression is Abundant in the Tumor Microenvironment and Indicates Poor Prognosis of Kidney Clear Cell Carcinoma

Cited by 5 publications

References 33 publications

TLR4 promoted endoplasmic reticulum stress induced inflammatory bowel disease via the activation of p38 MAPK pathway

TLR4 promoted endoplasmic reticulum stress induced inflammatory bowel disease via the activation of p38 MAPK pathway

Single-cell analysis reveals ADGRL4+ renal tubule cells as a highly aggressive cell type in clear cell renal cell carcinoma

Endoplasmic reticulum stress contributed to inflammatory bowel disease by activating p38 MAPK pathway

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