A New Approach to Morphological Evaluation of the Degree of Liver Fibrosis
In Experimental Animals

Developing liver disease treatments, in which fibrosis is a key pathogenetic link, still remains an urgent problem in hepatology. In the present study, the level of mmp-9 mRNA expression and the number of FAP+, -SMA+, CD45+ cells were analyzed at nine time points of fibrosis and cirrhosis. It was found that in the case of liver fibrosis, the choice of the optimal reference gene depended on the stage of fibrogenesis. When studying the specific stages rather than the entire process in a long-term experiment, it was shown that choosing an optimal reference gene has to be done additionally. In this case, the mmp-9 mRNA expression level should be considered as a marker of liver fibrosis initiation and development but not as that of cirrhosis progression. In the liver, two morphologically heterogeneous populations of myofibroblasts were simultaneously identified as able to synthesize various types of immunohistochemical markers. It was found that the FAP+ cells were the main contributor to the development of portal fibrosis and the initial stages of bridging fibrosis. In the selected experimental model, fibrosis initiation and the development stages preceding parenchyma restructuring were accompanied by a low level of inflammation.

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“…The degree of fibrosis was assessed using the semi-quantitative scale devised by K.G. Ishak ( Table 1 ) [ 22 , 23 ].…”

Section: Methodsmentioning

confidence: 99%

MMP-9 mRNA Expression and Bridging Fibrosis Progression in Toxic Liver Injury

Lebedeva¹,

Babenka²,

Shchastny³

2023

Acta Naturae

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Model of toxic fibrosis in Wistar rats: morphological and molecular-genetic parameters of the transition point to cirrhosis

Lebedeva,

Shchastniy,

Babenka

2023

Genes & Cells

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AIM: The aim of this work is to study the morphological and molecular genetic changes in the liver of Wistar rats during nodular parenchymal rearrangement. METHODS: Fibrosis and cirrhosis of the liver in male Wistar rats was induced with a freshly prepared solution of thioacetamide, which was administered intragastrically through a tube at a dose of 200 mg/kg of body weight 2 times a week for 13 weeks. The level of mRNA of the tweak (tnfsf12), fn14 (tnfrsf12a), ang, vegfa, cxcl12 (sdf), and mmp-9 genes in the liver was detected by real-time polymerase chain reaction. Immunohistochemical study was performed on paraffin sections. -SMA, FAP, CD68, CD206, CX3CR1, CD45 were used as markers. The area of interlobular veins and interlobular arteries was measured in m2. The number of sinusoidal capillaries and interlobular veins was counted. RESULTS: Based on the results obtained, it is possible to establish the transition point of fibrosis to cirrhosis as an independent separate stage of fibrogenesis. This transition was identified at stage F5, and the process itself - from F4 / F5 to F6. With the growth of fibrous tissue and nodular restructuring of the liver parenchyma, no progression of dystrophic processes and an increase in the zones of necrosis and necrobiosis of hepatocytes were noted. The number of -SMA+- and FAP+- cells in the period F4-F5 did not change (p=0,2073 and p=0,3775, respectively). At the same time, significant F6 cirrhosis was accompanied by an increase in their number by 1,50 times (p0,00001). Differences in the number of CD68+ cells were revealed only at the F4/F5 stage (2,0 times higher than the control, p0,00001). The number of CD206+-, CX3CR1+- and CD45+-cells remained the same. An increase in the number of interlobular veins (p0,00001) and a decrease in sinusoidal capillaries (p0,00001) were found compared to the control. The transition to cirrhosis was characterized by changes in the expression levels of tweak, fn14, ang, vegfa, cxcl12, and mmp-9 mRNAs, as well as the presence and strength of the relationship between them. Significant correlations were revealed between the target genes r=0.5-0.84 (p0.01).

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A New Approach to Morphological Evaluation of the Degree of Liver Fibrosis In Experimental Animals

Cited by 2 publications

References 13 publications

MMP-9 mRNA Expression and Bridging Fibrosis Progression in Toxic Liver Injury

MMP-9 mRNA Expression and Bridging Fibrosis Progression in Toxic Liver Injury

Model of toxic fibrosis in Wistar rats: morphological and molecular-genetic parameters of the transition point to cirrhosis

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