Changes in fibrosis markers from rat’s splenomegaly due to portal vein stenosis

Background and Aim: The spleen is the largest peripheral lymphoid organ in the body. Splenomegaly (SM) is a common complication of portal hypertension; however, the molecular mechanisms driving splenic fibrosis remain incompletely understood. Methods : This study established a portal vein stenosis–induced Sprague–Dawley (SM) rats (n = 20), with a sham-operated control (SO) group (n = 20). Splenic tissue fibrosis was evaluated using special staining techniques, including Masson, elastica van Gieson, and ammonia-silver staining. Matrix metallopeptidase 2 (MMP-2), MMP-9, tissue inhibitor of metalloproteinases 1 (TIMP-1), TIMP-2, transforming growth factor beta 1 (TGF-β1), and mothers against decapentaplegic homolog 7 (Smad7) were detected via immunohistochemistry, quantitative real-time polymerase chain reaction, and Western blotting. Results : In the SM group, microscopic observation revealed diffuse collagen proliferation, elastic fiber fragmentation, and reticular fiber densification. The proportions of MMP-2-, MMP-9-, TIMP-1-, TIMP-2-, TGF-β1-, and Smad7-positive cells were significantly higher than those in the SO group (P < 0.001). Gene and protein expressions of MMP-2, MMP-9, TIMP-1, TIMP-2, TGF-β1, and Smad7 were also significantly higher than those in the SO group (P < 0.001). Conclusion : In this rat model, portal vein stenosis–induced SM is associated with an imbalance in the MMP/TIMP ratio mediated by activation of the TGF-β1/Smad-signaling pathway. These results suggest potential molecular targets for antifibrotic therapeutic interventions.