Close homolog of L1-deficient ameliorates inflammatory bowel disease by regulating the balance of Th17/Treg

Yao, Jun; Gao, Ruoyu; Luo, Ming‐Han; Li, Defeng; Guo, Liliangzi; Yu, Zichao; Xiong, Feng; Wei, Cheng; Wu, Ben-Hua; Xu, Zefeng; Zhang, Dingguo; Wang, Jianyao; Wang, Lisheng

doi:10.1016/j.gene.2020.144931

Cited by 8 publications

(8 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The results indicated that CHL1 plays multitudinous roles in a variety of pathological models. Combined the previous results about the function of CHL1, the recent publication of a paper found that CHL1-deficient reduces the inflammatory response in 4% DSS-induced mice colitis, by regulating the balance of Th17/Treg in mice with colitis (Yao et al, 2020). In the present study, CHL1 may plays an anti-inflammation role initially in DSS-induced colitis, the increased of CHL1 attempts to reduce inflammation in WT mice colon.…”

Section: Discussionsupporting

confidence: 75%

Close Homolog of L1 Deficiency Exacerbated Intestinal Epithelial Barrier Function in Mouse Model of Dextran Sulfate Sodium-Induced Colitis

et al. 2020

View full text Add to dashboard Cite

The cell adhesion molecule CHL1, which belongs to the immunoglobulin superfamily, functions in a variety of physiological and pathological processes, including neural development, tissue injury, and repair. We previously found that the loss of CHL1 exacerbated the dextran sulfate sodium (DSS)-induced colitis in mice. In the present study, we further addressed the role of CHL1 in mouse model of DSS-induced colitis and its' potential mechanism. Colon tissues were collected from CHL1 +/+ , CHL1 +/− , and CHL1 −/− mice after DSS induction to investigate the effects of CHL1 on the development of colitis. The data showed that CHL1 was expressed in intestine tissue, and expression of CHL1 was increased by DSS-induced inflammation. CHL1 deficiency induced more pronounced colitis features, exacerbated inflammation, and damage to colonic tissues in DSS-induced mice. Moreover, colonic tissues of CHL1 −/− mice showed a marked increase in neutrophil and macrophage infiltration, be accompanied by more severe damage to intestinal epithelial cells and higher fluorescein isothiocyanate (FITC) leakage. Our results revealed deficiency of CHL1 exacerbated DSS-induced colitis, and this pathogenesis was potentially mediated by disruption of intestinal barrier integrity, indicating that CHL1 may be an attractive therapeutic target for inflammatory bowel diseases (IBDs) in mice.

show abstract

Section: Discussionsupporting

confidence: 75%

Close Homolog of L1 Deficiency Exacerbated Intestinal Epithelial Barrier Function in Mouse Model of Dextran Sulfate Sodium-Induced Colitis

et al. 2020

View full text Add to dashboard Cite

show abstract

“… 50 CHL1-deficient reduced recruitment of macrophages, inhibited Th17 cells differentiation and promoted Treg cells differentiation in IBD mice. 51 Taken together, NFASC and CHL1 may be involved in the immune dysregulation function of endometriosis. Our results suggested that NFASC and CHL1 were related to endometriosis progression and could serve as biomarkers for a novel potential strategy and a predictor for immunocyte infiltration in endometriosis.…”

Section: Discussionmentioning

confidence: 99%

Identification of NFASC and CHL1 as Two Novel Hub Genes in Endometriosis Using Integrated Bioinformatic Analysis and Experimental Verification

Chen¹,

Yao²,

Fang³

et al. 2022

PGPM

View full text Add to dashboard Cite

Background Endometriosis (EMS) is a common and highly recurrent gynecological disease characterized by chronic pain and infertility. There are no definitive therapies for endometriosis since the pathogenesis remains undetermined. This study aimed to identify EMS-related functional modules and hub genes by integrated bioinformatics analysis. Methods Three endometriosis expression profiling series (GSE25628, GSE23339, and GSE7305) were obtained from Gene Expression Omnibus (GEO). The EMS-related module was constructed by weighted gene co-expression network analysis (WGCNA), followed by Gene Ontology (GO) enrichment analyses. Cytohubba and the MCODE plug-ins of Cytoscape were used to screen out the hub genes, which were verified via receiver operating characteristic (ROC) curves. Immunohistochemistry was performed to verify the protein expression of the hub genes in ectopic endometrial tissues. Moreover, CIBERSORT was used to analyze the relationship between the abundance of immune cells infiltration and the expression of hub genes. Results Among the 18 modules obtained, the darkmagenta module was identified as the EMS-related module, genes of which were significantly enriched to terms referring to cell migration and neurogenesis. NFASC and CHL1 were screened out and prioritized as hub genes through Cytoscape and confirmed to be differentially upregulated in ectopic endometrial samples. Finally, the expression of hub genes was related to the abundance of immune cells infiltration. The higher expression of NFASC or CHL1 correlated with increased M2 macrophages and decreased natural killer (NK) cells in ectopic lesions. Conclusion This study provided new insights into the molecular factors underlying the pathogenesis of endometriosis and provided a theoretical basis for the potential that the two hub genes, NFASC and CHL1, might be novel biomarkers and therapeutic targets in the future.

show abstract

“…Also, dextran sulfate-induced colitis was reported to lead to exacerbated in ammation and damage to colonic tissues of CHL1-/-mice with an increased neutrophil and macrophage in ltration [18]. In contrast, another group reported an attenuated in ammatory response of CHL1-/-mice in a dextran sulfate-induced in ammatory bowel disease mouse model [19]. However, the two studies did not indicate the sex of mice used.…”

Section: Discussionmentioning

confidence: 99%

CHL1-deficient and wild-type male mice do not differ in locomotor recovery from spinal cord injury

Schachner

Theis

Ayala

et al. 2022

Preprint

View full text Add to dashboard Cite

STUDY DESIGNAnimal studyOBJECTIVESFemale mice deficient in the adhesion molecule CHL1 recovered better than their wild-type female littermates after spinal cord injury (SCI). This observation was unexpected, because CHL1 increases neurite outgrowth in vitro in a homophilic, neuron-dependent manner. Yet, in SCI, CHL1 is upregulated in the glial scar which reduces axonal regrowth, showing that CHL1 on glia can block regrowth of CHL1 positive axons. This notion that was verified in co-cultures of astrocytes and neurons. Since these SCI experiments were confined to females in the previous study, we now sought to assess SCI in CHL1-deficient male mice.SETTINGSW.M. Keck Center for Collaborative Neuroscience at RutgersMETHODSMale CHL1-deficient and wild-type littermate mice received thoracic weight-drop SCI. Locomotor recovery was analyzed weekly by the Basso Mouse Scale and a single frame motion analysis up to six weeks after SCI, when lesion volumes were measured immunohistologically. Hematological analysis was performed at 24 hours after injury.RESULTSCHL1-deficient males did not recover better or worse than their male wild-type littermates. Primary and secondary lesion volumes were similar in the two genotypes under all conditions. In the peripheral blood at 24 h after SCI, leukocyte numbers in mutant males were slightly higher than in wild-type males, but monocyte and lymphocyte numbers did not differ between genders. Neutrophil numbers were higher in males than in females.CONCLUSIONThese results indicate that CHL1-deficient males and females differ in the number of neutrophils slightly in numbers of leukocytes, but not lymphocytes or monocytes.

show abstract

Close homolog of L1-deficient ameliorates inflammatory bowel disease by regulating the balance of Th17/Treg

Cited by 8 publications

References 40 publications

Close Homolog of L1 Deficiency Exacerbated Intestinal Epithelial Barrier Function in Mouse Model of Dextran Sulfate Sodium-Induced Colitis

Close Homolog of L1 Deficiency Exacerbated Intestinal Epithelial Barrier Function in Mouse Model of Dextran Sulfate Sodium-Induced Colitis

Identification of NFASC and CHL1 as Two Novel Hub Genes in Endometriosis Using Integrated Bioinformatic Analysis and Experimental Verification

CHL1-deficient and wild-type male mice do not differ in locomotor recovery from spinal cord injury

Contact Info

Product

Resources

About