Background and aim: Previous studies have revealed significantly increased levels of plasma and mucosal homocysteine (Hcy) in patients with Crohn's disease (CD); however, whether Hcy is involved in intestinal fibrosis of CD remains unclear. This study aimed to investigate the effects of Hcy on intestinal fibrosis in TNBS/ethanol-induced colitis and to elucidate its potential mechanisms.
Methods: Sprague-Dawley rats were divided into 4 groups: normal control, normal + Hcy injection, TNBS model and TNBS model + Hcy injection. Hyperhomocysteinemia was induced by subcutaneous injection of Hcy. DAI, CMDI and HI were calculated to evaluate the severity of colitis. Masson trichrome staining was performed to assess the severity of fibrosis. The plasma and mucosal levels of Hcy were measured by HPLC-FD. The levels of IL-1β, IL-6, TNF-α, TGF-β1, CTGF, MMP-2,9 and collagen I, III in the colon were determined by ELISA, and the mRNA expressions of TGF-β1, MMP-2,9 and TIMP-1 were detected by RT-PCR.
Results: Hcy was found to increase the scores of DAI, CMDI and HI; levels of IL-1β, Il-6, TNF-α, TGF-β1, CTGF, MMP-2,9 and collagen I, III; and mRNA expressions of TGF-β1, MMP-2,9 and TIMP-1 in colonic tissue of rats with TNBS/ethanol-induced colitis.
Conclusions: Hcy promotes intestinal fibrosis in rats with TNBS/ethanol-induced colitis, the underlying mechanisms of which may be attributed to its effects of increasing inflammatory damage, promoting the expression of profibrogenic cytokines and influencing MMPs/TIMPs balance.