Digestive Diseases and Sciences

, Volume 63, Issue 11, pp 2910–2922 | Cite as

Disruption of GPR35 Exacerbates Dextran Sulfate Sodium-Induced Colitis in Mice

  • Shukkur M. Farooq
  • Yuning Hou
  • Hainan Li
  • Megan O’Meara
  • Yihan Wang
  • Chunying LiEmail author
  • Jie-Mei WangEmail author
Original Article



G protein-coupled receptor 35 (GPR35) is an orphan receptor and is vastly expressed in immune cells and gastrointestinal cells, suggesting the potential physiological importance of GPR35 in these cells. Here, we tested the hypothesis that the lack of GPR35 expression in the colon mucosa exacerbates the severity of dextran sulfate sodium (DSS)-induced experimental colitis in mice.


Colitis was induced in GPR35 wild-type (GPR35+/+) and GPR35 knockout (GPR35−/−) mice through the administration of DSS in drinking water for 5 days followed by regular facility water for 1 day. Induction of colitis was evaluated by measuring relative body weight loss, clinical illness scores, and morphological changes in the colon. Abolition of Gpr35 gene expression in the colon mucosa of GPR35−/− mice was confirmed by quantitative real-time PCR (qPCR). Gene expressions of inflammatory and tissue remodeling cytokines were detected by qPCR. Human colorectal epithelial Caco cells were transfected with siRNA against GPR35 before treated with 1% DSS in vitro. Protein expressions were measured using Western blot.


GPR35−/− mice receiving DSS showed a significantly worsened colitis disease with profound loss of body weight and a considerable amount of severe clinical illness compared to GPR35+/+ mice that received DSS. The histology of colon sections from GPR35−/− mice showed extensive pathological changes including submucosal edema, diffuse ulcerations, and evidence of complete loss of crypts compared to wild-type mice. The mean histopathological score was significantly higher in GPR35−/− mice as compared to GPR35+/+ mice. The qPCR data revealed significant expression of pro-inflammatory and tissue remodeling cytokines in GPR35−/− colon mucosa, including IL-1β, CXCL1, CXCL2, CCL2, HMGB1, TGFβ1, TGFβ3, MMP1/9/12. The protein expressions of Zonula occludens-1, E-cadherin, Claudin1 were decreased upon knocking down GPR35 with or without 1% DSS treatment.


Our experimental data suggest that lack of GPR35 resulted in worsened disease outcome in DSS-induced experimental colitis, indicating that GPR35 could play a crucial role in protecting from colonic inflammation and serve as a therapeutic target.


G protein-coupled receptor 35 Inflammatory bowel disease Colitis Dextran sulfate sodium Colon inflammation 



Complementary deoxyribonucleic acid


C-X-C motif chemokine 17


Dextran sulfate sodium


G protein-coupled receptor 35

HEK 293 cells

Human embryonic kidney cells 293




Kynurenic acid


Lysophosphatidic acid


Polymerase chain reaction


Ribonucleic acid


Wild type



We thank the Wellcome Trust Sanger Institute Mouse Genetics Project (Sanger MGP) and its funders for providing the mutant mouse line (Allele: GPR35) and INFRAFRONTIER/EMMA ( Funding information may be found at and associated primary phenotypic information at


This work was supported in part by American Heart Association Scientist Development Grant 13SDG16930098 (to J.M.W.), NIH/NIDDK R01 DK109036 (To J.M.W.), Wayne State University Faculty Start-up Fund (To J.M.W.), and NIH/NHLBI R01 HL128647 (To C.L.).

Compliance with ethical standards

Conflict of interest

No conflicts of interest, financial or otherwise, are declared by the authors.

Supplementary material

10620_2018_5216_MOESM1_ESM.docx (144 kb)
Supplementary material 1 (DOCX 143 kb)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Shukkur M. Farooq
    • 1
  • Yuning Hou
    • 2
  • Hainan Li
    • 1
  • Megan O’Meara
    • 1
  • Yihan Wang
    • 1
  • Chunying Li
    • 2
    Email author
  • Jie-Mei Wang
    • 1
    • 3
    Email author
  1. 1.Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health SciencesWayne State UniversityDetroitUSA
  2. 2.Center for Molecular and Translational Medicine, Research Science Center BuildingGeorgia State UniversityAtlantaUSA
  3. 3.Centers for Molecular Medicine and Genetics, Karmanos Cancer InstituteWayne State UniversityDetroitUSA

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