Dynamics of distribution of vimentin and alpha-smooth muscle actin in the liver at the stages of regeneration after chemically induced fibros

The aim of the study was to analyze the distribution of vimentin and alpha-smooth muscle actin (α-SMA) in the liver at various stages of regeneration after chemically induced fibrosis. Material and methods. Four experimental groups of animals were formed, consisting of white male rats representing different stages of liver recovery (no recovery, 4, 8, and 12 weeks of recovery) after chemically induced liver fibrosis, and a control group of intact animals, with 8 animals in each group. The dynamics of the distribution of intermediate filaments of mesenchymal cells were analyzed on preparations stained by immunohistochemical method using antibodies to vimentin and α-SMA. Results. After chemically induced liver fibrosis, a significant increase in the specific area of vimentin and α-SMA was observed, suggesting an important role of mesenchymal cells in the remodeling of the liver parenchyma. At the 4th week, the increased number of vimentin- and α-SMA-positive cells persisted, with these cells localized along fibrous septa and around blood vessels. At this stage, regenerative rosette-like structures consisting of vimentin- and α-SMA-positive mesenchymal cells surrounded by young regenerating hepatocytes were formed. By the 8^th–12^th weeks of regeneration, a decrease in the specific area of these markers was noted; however, vimentin- and α-SMA-positive cells were still present near portal triads and blood vessels, indicating ongoing regeneration processes. Conclusion. Vimentin and α-SMA play a key role in the formation of the fibrous matrix and the activation of perisinusoidal cells and myofibroblasts. The observed correlation between changes in vimentin and α-SMA indicates their coordinated involvement in the processes of fibrosis and regeneration.  

1. Friedman SL. Liver fibrosis – from bench to bed-side. Journal of Hepatology. 2003 Jan;38:38–53. doi: 10.1016/s0168-8278(02)00429-4

2. Kisseleva T, Cong M, Paik Y, Scholten D, Jiang C, Benner C, et al. Myofibroblasts revert to an inactive phenotype during regression of liver fibrosis. Proceedings of the National Academy of Sciences. 2012 May 7;109(24):9448–53. doi: 10.1073/pnas.1201840109

3. Li J, Xin J, Zhang L, Wu J, Jiang L, Zhou Q, et al. Human Hepatic Progenitor Cells Express Hematopoietic Cell Markers CD45 and CD109. International Journal of Medical Sciences. 2014;11(1):65–79.

4. Lieber CS. Alcoholic liver disease: New insights in pathogenesis lead to new treatments. Journal of Hepatology. 2000 Jan;32:113–28. doi: 10.1016/s0168-8278(00)80420-1

5. Marin F, Boya J, A. Lopez-Carbonell. Immunocytochemical localization of vimentin in stellate cells (Folliculo-stellate cells) of the rat, cat and rabbit pituitary pars distalis. Anatomy and embryology. 1989 Apr 1;179(5):491–5. doi: 10.1007/bf00319592

6. Pervin M, Hasan I, Kobir MdA, Akter L, Karim MR. Immunophenotypic analysis of the distribution of hepatic macrophages, lymphocytes and hepatic stellate cells in the adult rat liver. Anatomia, Histologia, Embryologia. 2021 Jun 15;50(4):736–45. doi: 10.1111/ahe.12718

7. Ramachandran P, Iredale J, Fallowfield J. Resolution of Liver Fibrosis: Basic Mechanisms and Clinical Relevance. Seminars in Liver Disease. 2015 May 14;35(02):119–31. doi: 10.1055/s-0035-1550057

8. Tsuchida T, Friedman SL. Mechanisms of hepatic stellate cell activation. Nature Reviews Gastroenterology & Hepatology. 2017 May 10;14(7):397–411. doi: 10.1038/nrgastro.2017.38

9. Zeisberg M, Yang C, Martino M, Duncan MB, Rieder F, Tanjore H, et al. Fibroblasts Derive from Hepatocytes in Liver Fibrosis via Epithelial to Mesenchymal Transition. Journal of Biological Chemistry. 2007 Aug;282(32):23337–47. doi: 10.1074/jbc.m700194200

10. Hong Z, Reeves KJ, Sun Z, Li Z, Brown NJ, Meininger GA. Vascular Smooth Muscle Cell Stiffness and Adhesion to Collagen I Modified by Vasoactive Agonists. Dague E, editor. PLOS ONE. 2015 Mar 6;10(3):e0119533. doi: 10.1371/journal.pone.0119533