Gum Arabic Supplementation Suppresses Colonic Fibrosis After Acute Colitis by Reducing Transforming Growth Factor ß1 Expression.

Ulcerative colitis is a chronic inflammation of the colonic mucosa. Gum Arabic (GA) has been reported to exert anti-inflammatory and antifibrotic activity. This study aimed to evaluate the effect of GA on disease activity in an experimental model of colitis. Dextran sodium sulfate (DSS) was used to induce colitis in C57BL/6 mice and the animals were then switched to normal drinking water to monitor recovery. Mice received 140 g/L GA before (pre-GA group) or after (post-GA group) induction of colitis. Disease activity and recovery were assessed by changes in body weight, disease activity index (DAI), and histological assessment. Gene expression of proinflammatory, anti-inflammatory, and fibrotic markers was measured in colonic tissues. Mice in the pre-GA group showed an increase in body weight, with no differences in DAI scores, during the recovery phase and had lower histological colitis scores than mice in the post-GA group, which showed higher DAI and histological scores during the recovery phase. During the recovery phase, mice in the pre-GA group showed increased expression of proinflammatory markers, while gene expression of the fibrotic markers, transforming growth factor ß1 (TGFß1) and procollagen I, was reduced. The reduced fibrotic marker expression was associated with reduced collagen staining and increased epithelial cell proliferation. Administration of GA had protective and alleviative effects on the severity of DSS-induced colitis, with a reduction in colonic fibrosis and TGFß1 expression. These data warrant further in vitro and in vivo investigations on the effect of GA on fibroblast activity.

Deletion of SOCS2 Reduces Post-Colitis Fibrosis via Alteration of the TGFß Pathway.

Inflammatory bowel disease (IBD) is an immunologically mediated chronic intestinal disorder. Growth hormone (GH) administration enhances mucosal repair and decreases intestinal fibrosis in patients with IBD. In the present study, we investigated the effect of cellular sensitivity to GH via suppressor of cytokine signaling 2 (SOCS2) deletion on colitis and recovery. To induce colitis, wild type and SOCS2 knockout (SOCS2-/-) mice were treated with 3% dextran sodium sulphate (DSS), followed by a recovery period. SOCS2-/- mice showed higher disease activity during colitis with increased mRNA expression of the pro-inflammatory cytokines nitric oxide synthase 2 (NOS2) and interleukin 1 ß (IL1-ß). At recovery time point, SOCS2-/- showed better recovery with less fibrosis measured by levels of α-SMA and collagen deposition. Protein and mRNA expressions of transforming growth factor beta ß1 (TGF-ß1) receptors were significantly lower in SOCS2-/- mice compared to wild-type littermates. Using an in vivo bromodeoxyuridine (BrdU) proliferation assay, SOCS2-/- mice showed higher intestinal epithelial proliferation compared to wild-type mice. Our results demonstrated that deletion of the SOCS2 protein results in higher growth hormone sensitivity associated with higher pro-inflammatory signaling; however, it resulted in less tissue damage with less fibrotic lesions and higher epithelial proliferation, which are markers of GH-protective effects in IBD. This suggests a pleiotropic effect of SOCS2 and multiple cellular targets. Further study is required to study role of SOCS2 in regulation of TGFß-mothers against the decapentaplegic homolog (Smad) pathway.