Stromal C-type lectin receptor COLEC12 integrates H. pylori, PGE2-EP2/4 axis and innate immunity in gastric diseases

Chang, Lin; Hsu, Wen Hung; Kao, Mou Chieh; Chou, Chih-Chung; Lin, Chung Cheng; Liu, Chung‐Jung; Weng, Bi Chuang; Kuo, Fu Chen; Kuo, Chun Hong; Lin, Ming Hong; Wang, Chun Jen; Lin, Chun Hung; Wu, Deng Chyang; Huang, Shau Ku

doi:10.1038/s41598-018-20957-2

Cited by 29 publications

(24 citation statements)

References 47 publications

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“…High MMP7 expression facilitated cancer invasion and angiogenesis by degrading extracellular matrix macromolecules and connective tissues in vivo. Recently, the direct interaction between this bacterial pathogen and fibroblasts has been proposed16 suggesting that H. pylori can interact with several components of connective tissue components including fibroblasts. The most virulent H. pylori strains have been shown to harbor the cag pathogenicity island encoding the type IV secretion system,3, 17 allowing the delivery of bacterial cytotoxins into gastric epithelial cells, inducing phenotypic alterations reminiscent of an epithelial to mesenchymal transition (EMT) 3, 17, 18, 19…”

Section: Introductionmentioning

confidence: 99%

Role of Helicobacter pylori infection in cancer‐associated fibroblast‐induced epithelial‐mesenchymal transition in vitro

et al. 2018

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BackgroundMajor human gastrointestinal pathogen Helicobacter pylori (H. pylori) colonizes the gastric mucosa causing inflammation and severe complications including cancer, but the involvement of fibroblasts in the pathogenesis of these disorders in H. pylori‐infected stomach has been little studied. Normal stroma contains few fibroblasts, especially myofibroblasts. Their number rapidly increases in the reactive stroma surrounding inflammatory region and neoplastic tissue; however, the interaction between H. pylori and fibroblasts remains unknown. We determined the effect of coincubation of normal rat gastric fibroblasts with alive H. pylori (cagA+vacA+) and H. pylori (cagA−vacA−) strains on the differentiation of these fibroblasts into cells possessing characteristics of cancer‐associated fibroblasts (CAFs) able to induce epithelial‐mesenchymal transition (EMT) of normal rat gastric epithelial cells (RGM‐1).Materials and MethodsThe panel of CAFs markers mRNA was analyzed in H. pylori (cagA+vacA+)‐infected fibroblasts by RT‐PCR. After insert coculture of differentiated fibroblasts with RGM‐1 cells from 24 up to 48, 72, and 96 hours, the mRNA expression for EMT‐associated genes was analyzed by RT‐PCR.ResultsThe mRNA expression for CAFs markers was significantly increased after 72 hours of infection with H. pylori (cagA+vacA+) but not H. pylori (cagA−vacA−) strain. Following coculture with CAFs, RGM‐1 cells showed significant decrease in E‐cadherin mRNA, and the parallel increase in the expression of Twist and Snail transcription factors mRNA was observed along with the overexpression of mRNAs for TGFβR, HGFR, FGFR, N‐cadherin, vimentin, α‐SMA, VEGF, and integrin‐β1.Conclusion Helicobacter pylori (cagA+vacA+) strain induces differentiation of normal fibroblasts into CAFs, likely to initiate the EMT process in RGM‐1 epithelial cell line.

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Section: Introductionmentioning

confidence: 99%

Role of Helicobacter pylori infection in cancer‐associated fibroblast‐induced epithelial‐mesenchymal transition in vitro

et al. 2018

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“…pylori-gastric stromal cells interaction and mediating crosstalk between these cells and dendritic cells (28). Finally, and particularly important for the background of this study, surface-bound CL-12 has been suggested to play a role in complement activation through the classical pathway via its association with C-reactive protein and C1q (29).…”

Section: Introductionmentioning

confidence: 78%

Soluble collectin-12 mediates C3-independent docking of properdin that activates the alternative pathway of complement

Zhang

Song

Pedersen

et al. 2020

eLife

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Properdin stabilizes the alternative C3 convertase (C3bBb), whereas its role as pattern recognition molecule mediating complement activation is disputed for decades. Previously, we have found that soluble collectin-12 (sCL-12) synergizes complement alternative pathway (AP) activation. However, whether this observation is C3 dependent is unknown. By application of the C3-inhibitor Cp40, we found that properdin in normal human serum bound to Aspergillus fumigatus solely in a C3b dependent manner. Cp40 also prevented properdin binding when properdin-depleted serum reconstituted with purified properdin was applied, in analogy with the findings achieved by C3- depleted serum. However, when opsonized with sCL-12, properdin bound in a C3-independent manner exclusively via its tetrameric structure and directed in situ C3bBb assembly. In conclusion, a prerequisite for properdin binding and in situ C3bBb assembly was the initial docking of sCL-12. This implies a new important function of properdin in host defence bridging pattern recognition and specific AP activation.

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“…In addition, dysregulation of C4A, and GPS2, are also known to be involved in the development of leukemia in humans when they are dysregulated (30,31). The gene COLEC12 produces a receptor that mediates the crosstalk between dendritic cells and gastric stromal cells and has been associated with the development of gastric cancer patients when deregulated (32). BLV miRNAs seem to dysregulate the expression genes to proliferate in cattle.…”

Section: Discussionmentioning

confidence: 99%

Expression of Viral microRNAs in Serum and White Blood Cells of Cows Exposed to Bovine Leukemia Virus

Casas

Lippolis

2020

Front. Vet. Sci.

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Bovine leukemia virus (BLV) affects the health and productivity of cattle. The virus causes abnormal immune function and immunosuppression. MicroRNAs (miRNAs) are involved in gene expression, having been associated with stress and immune response, tumor growth, and viral infection. The objective of this study was to determine the expression of circulating miRNAs produced by BLV in animals exposed to the virus. Sera from 14 animals were collected to establish IgG reactivity to BLV by ELISA, where seven animals were seropositive and seven were seronegative for BLV exposure. White blood cells (WBC) from each animal were also collected and miRNAs were identified by sequencing from sera and WBC. The seropositive group had higher counts of BLV miRNAs when compared to seronegative group in sera and WBC. Blv-miR-1-3p, blv-miR-B2-5p, blv-miR-B4-3p, and blv-miR-B5-5p were statistically significant (P < 0.00001) in serum with an average of 7 log2 fold difference between seropositive and seronegative groups. Blv-miR-B1-3p, blv-miR-B1-5p, blv-miR-B3, blv-miR-B4-3p, blv-miR-B4-5p, blv-miR-B5-5p were statistically significant (P < 1.08e −9) in WBC with an average of 7 log2 fold difference between the seropositive and the seronegative groups. Blv-miR-B2-3p and blv-miR-B2-5p were also statistically significant in WBC (P < 2.79e-17), with an average of 27 log2 fold difference between the seropositive and the seronegative groups. There were 18 genes identified as being potential targets for blv-miR-B1-5p, and 3 genes for blv-miR-B4-5p. Gene ontology analysis indicated that the target genes are mainly involved in the response to stress and in the immune system process. Several of the identified genes have been associated with leukemia development in humans and cattle. Differential expression of genes targeted by BLV miRNAs should be evaluated to determine their effect in BLV replication.

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Stromal C-type lectin receptor COLEC12 integrates H. pylori, PGE2-EP2/4 axis and innate immunity in gastric diseases

Cited by 29 publications

References 47 publications

Role of Helicobacter pylori infection in cancer‐associated fibroblast‐induced epithelial‐mesenchymal transition in vitro

Role of Helicobacter pylori infection in cancer‐associated fibroblast‐induced epithelial‐mesenchymal transition in vitro

Soluble collectin-12 mediates C3-independent docking of properdin that activates the alternative pathway of complement

Expression of Viral microRNAs in Serum and White Blood Cells of Cows Exposed to Bovine Leukemia Virus

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