Expression of the novel adipokine C1qTNF-related protein 4 (CTRP4) suppresses colitis and colitis-associated colorectal cancer in mice

Abstract

Inflammatory bowel disease (IBD) is an important factor in the induction of colon cancer, but its mechanism is unclear. Colitis and colitis-associated colorectal cancer (CAC) models induced using both dextran sulfate sodium (DSS) and the azoxymethane/DSS protocol were established in wild-type (WT) and CTRP4 transgenic (CTRP4-tg) C57BL6/J mice. Body weight, stool consistency and the presence of blood in the stool were analyzed; tumor quantity, size and histological characteristics were analyzed during the development of CAC. The CTRP4-tg mice exhibited significantly reduced colitis and developed far fewer macroscopic tumors; these tumors were smaller in size, and a majority of the colon tumors in these mice were restricted to the superficial mucosa. Tumors of lower grades were observed in the CTRP4-tg mice. Interleukin-6 was markedly downregulated in the CTRP4-tg mice during CAC tumorigenesis. The phosphorylation of ERK, signal transducer and activator of transcription 3 and Akt in the colon and the proliferation of intestinal epithelial cells were decreased in the CTRP4-tg mice. The injection of recombinant CTRP4 protein significantly reduced the colitis symptoms of the WT mice. CTRP4 plays an important role in inflammation and inflammation-associated colon tumorigenesis, and our research may provide a novel method for the treatment of IBD and CAC.

Protective Effect of Protocatechuic Acid on TNBS-Induced Colitis in Mice Is Associated with Modulation of the SphK/S1P Signaling Pathway

“…In murine models of DSS Rosmarinus officinalis extract ameliorates intestinal inflammation through MAP kinases/NF-κB signaling [39]. It is also known that expression of the novel adipokine CTRP4 suppresses colitis in mice with a marked downregulation of ERK, AKT and STAT3 [40]. Abrogation of the upregulation of the upstream kinases AKT and ERK could therefore play a role in the SphK/S1P-mediated anti-inflammatory effects of PCA.…”

Adipose tissue-derived cytokines, CTRPs as biomarkers and therapeutic targets in metabolism and the cardiovascular system

“…Regulates glucose and lipid metabolism regulates systemic inflammation in obesity and insulin resistance; modulates mitochondrial biogenesis; attenuate liver fibrosis; biomarker for diabetic retinopathy; negative regulator of osteoclastogenesis; independent predictor for atherosclerosis [47,[56][57][58][59][60] 4 Hepatic cells Modulates energy metabolism; novel nutrient-responsive central regulator of food intake and energy balance; reduces colitis; suppresses the pyroptosis of trophoblasts derived from rats with preeclampsia [61][62][63] 5 Adipose tissue, ocular tissue…”

NLR members in inflammation-associated carcinogenesis

“…Establishment of an inflammatory state is crucial for colitis-associated carcinogenesis. 16 To assess the inflammatory state of the Nlrc3-/mice treated with AOM/DSS, Karki et al 13 examined the expression of inflammatory cytokines, inflammatory signaling pathways and immune cell infiltration in colon tissues at days 80 and 14, which was 3 days after the first round of DSS treatment. There were no significant differences at day 80 between the Nlrc3-/mice and WT mice.…”