Impact of hepatic E-cadherin overexpression on liver fibrosis in mice infected with Schistosoma japonicum

doi:10.12140/j.issn.1000-7423.2026.01.003

Abstract

Abstract:

Objective To investigate the impact of E-cadherin (E-cad) overexpression on hepatic epithelial-mesenchymal transition (EMT) and liver fibrosis induced by Schistosoma japonicum infection. Methods A total of 16 mice were randomly divided into the E-cad group and the control group, and were injected with 2 × 10¹¹ vector genomes of E-cad plasmid or empty plasmid packaged with adeno-associated virus 8 via the tail vein. All mice were infected with S. japonicum cercariae [(20 ± 1) per mouse] via the abdomen 3 weeks post-injection, and liver tissues were collected 6 weeks post-infection. Total RNA was extracted from liver tissues, and the relative transcription levels of target genes were detected with a real-time quantitative PCR (qPCR) assay. Total protein was extracted from liver tissues, and the relative expression of target proteins was detected using Western blotting. Paraffin-embedded liver sections were stained with hematoxylin and eosin (HE) and Masson’s trichrome stains to assess the area of single-egg granulomas and collagen fibers. All statistical analyses were performed using the software GraphPad Prism 9, and differences of means between groups were assessed using t-test. Results The relative mRNA transcription levels of E-cad were 1.15 ± 0.07 and 7.19 ± 2.43 in mouse liver tissues in the control and E-cad group (t = 4.30, P < 0.05), and the relative protein expression of E-cad were 1.03 ± 0.16 and 1.42 ± 0.22 in the control and E-cad group (t = 3.62, P < 0.01), indicating successful modeling of hepatic E-cad overexpression in mice. qPCR assay quantified lower relative mRNA transcription of vimentin (Vim) [(0.60 ± 0.17) vs. (1.37 ± 0.33); t = 3.60, P < 0.05], α-smooth muscle actin (α-SMA) [(0.62 ± 0.19) vs. (1.43 ± 0.35); t = 3.48, P < 0.05], collagenⅠ (Col-1) [(0.31 ± 0.17) vs. (1.78 ± 0.84); t = 3.74, P < 0.05] and collagenⅢ (Col-3) [(0.30 ± 0.13) vs. (1.78 ± 0.45); t = 5.52, P < 0.01] in mouse liver tissues in the E-cad group than in the control group, and Western blotting determined lower relative expression of Vim [(0.22 ± 0.13) vs. (0.71 ± 0.13); t = 4.39, P < 0.01], N-cadherin (N-cad) [(0.37 ± 0.14) vs. (0.65 ± 0.08); t = 2.75, P < 0.05], α-SMA [(0.29 ± 0.19) vs. (0.81 ± 0.13); t = 3.91, P < 0.01], Col-1 [(0.23 ± 0.06) vs. (0.43 ± 0.08); t = 3.99, P < 0.01], Col-3 [(0.17 ± 0.02) vs. (0.50 ± 0.16); t = 3.47, P < 0.05], transforming growth factor-β1 (TGF-β1) [(0.32 ± 0.13) vs. (0.68 ± 0.07); t = 3.92, P < 0.01], Smad2 [(0.57 ± 0.14) vs. (0.87 ± 0.04); t = 2.95, P < 0.05] and Smad3 [(0.54 ± 0.10) vs. (0.82 ± 0.06); t = 4.61, P < 0.05] in mouse liver tissues in the E-cad group than in the control group. HE staining showed that the area of single-egg liver granulomas were [(34.10 ± 6.94) × 10⁴] and [(12.76 ± 3.16) × 10⁴] μm² in the control and E-cad groups (t = 7.41, P < 0.01), and Masson staining showed that the areas of collagen fibers with single-egg liver granulomas were [(8.50 ± 2.36) × 10⁴] and [(3.65 ± 0.90) × 10⁴] μm² in the control and E-cad groups (t = 5.01, P < 0.01), respectively. Conclusion Hepatic E-cad overexpression alleviates EMT and liver fibrosis induced by S. japonicum infection in mice, potentially through inhibition of the TGF-β1/Smad signaling pathway.

Key words: Schistosoma japonicum, E-cadherin, Epithelial-mesenchymal transition, Liver fibrosis, TGF-β1/Smad signaling pathway

CLC Number:

R532.21

JIANG Tingting, YU Zhihao, CUI Xuanyin, MO Xiaojin, LI Xian, HU Yuan. Impact of hepatic E-cadherin overexpression on liver fibrosis in mice infected with Schistosoma japonicum[J]. CHINESE JOURNAL OF PARASITOLOGY AND PARASITIC DISEASES, 2026, 44(1): 15-20.

Figures/Tables 6

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References 23

[1]	Buonfrate D, Ferrari TCA, Adegnika AA, et al. Human schistosomiasis[J]. Lancet, 2025, 405(10479): 658-670.
[2]	LoVerde PT. Schistosomiasis[J]. Adv Exp Med Biol, 2024, 1454: 75-105.
[3]	钟昊然, 金亚美. 日本血吸虫病肝纤维化的研究进展[J]. 中国动物传染病学报, 2023, 31(6): 177-183.
	Zhong HR, Jin YM. Advance on liver fibrosis induced by Schistosoma japonicum infection[J]. Chin J Vet Parasitol, 2023, 31(6): 177-183. (in Chinese)
[4]	何君逸, 张利娟, 杨帆, 等. 2024年全国血吸虫病防治进展[J]. 中国血吸虫病防治杂志(中英文), 2025, 37(3): 223-231.
	He JY, Zhang LJ, Yang F, et al. Progress of schistosomiasis control in the people’s republic of China in 2024[J]. Chin J Schisto Control, 2025, 37(3): 223-231. (in Chinese)
[5]	Liu ZL, Zhang LC, Liang YM, et al. Pathology and molecular mechanisms of Schistosoma japonicum-associated liver fibrosis[J]. Front Cell Infect Microbiol, 2022, 12: 1035765.
[6]	Marconi GD, Fonticoli L, Rajan TS, et al. Epithelial-mesenchymal transition (EMT): the type-2 EMT in wound healing, tissue regeneration and organ fibrosis[J]. Cells, 2021, 10(7): 1587.
[7]	Zhu W, Zhu ZX, Feng J, et al. PRAG1 promotes cholangiocyte epithelial-mesenchymal transition and liver fibrosis in biliary atresia[J]. Biochim Biophys Acta Mol Basis Dis, 2025, 1871(8): 167994.
[8]	Chu AS, Diaz R, Hui JJ, et al. Lineage tracing demonstrates no evidence of cholangiocyte epithelial-to-mesenchymal transition in murine models of hepatic fibrosis[J]. Hepatology, 2011, 53(5): 1685-1695.
[9]	Chen J, Ge SJ, Feng HJ, et al. KRT17 promotes the activation of HSCs via EMT in liver fibrosis[J]. J Clin Transl Hepatol, 2022, 10(2): 207-218.
[10]	McManus DP, Bergquist R, Cai PF, et al. Schistosomiasis―from immunopathology to vaccines[J]. Semin Immunopathol, 2020, 42(3): 355-371.
[11]	Perera DJ, Koger-Pease C, Paulini K, et al. Beyond schistosomiasis: unraveling co-infections and altered immunity[J]. Clin Microbiol Rev, 2024, 37(1): e00098-e00023.
[12]	Sisto M, Ribatti D, Lisi S. Organ fibrosis and autoimmunity: the role of inflammation in TGFβ-dependent EMT[J]. Biomolecules, 2021, 11(2): 310.
[13]	Kumar V, Xin XF, Ma JY, et al. Therapeutic targets, novel drugs, and delivery systems for diabetes associated NAFLD and liver fibrosis[J]. Adv Drug Deliv Rev, 2021, 176: 113888.
[14]	Zhang XX, Chen JC, Lin RH, et al. Lactate drives epithelial-mesenchymal transition in diabetic kidney disease via the H3K14la/KLF5 pathway[J]. Redox Biol, 2024, 75: 103246.
[15]	Li MD, Chen LH, Xiang HX, et al. Benzo [a] pyrene evokes epithelial-mesenchymal transition and pulmonary fibrosis through AhR-mediated Nrf2-p62 signaling[J]. J Hazard Mater, 2024, 473: 134560.
[16]	Shu GW, Yusuf A, Dai CX, et al. Piperine inhibits AML-12 hepatocyte EMT and LX-2 HSC activation and alleviates mouse liver fibrosis provoked by CCl(4): roles in the activation of the Nrf2 cascade and subsequent suppression of the TGF-β1/Smad axis[J]. Food Funct, 2021, 12(22): 11686-11703.
[17]	Kong C, Qu XZ, Liu MM, et al. Dynamic interactions between E-cadherin and Ankyrin-G mediate epithelial cell polarity maintenance[J]. Nat Commun, 2023, 14(1): 6860.
[18]	Nakagawa H, Hikiba Y, Hirata Y, et al. Loss of liver E-cadherin induces sclerosing cholangitis and promotes carcinogenesis[J]. Proc Natl Acad Sci USA, 2014, 111(3): 1090-1095.
[19]	Jiang TT, Wu XY, Zhou H, et al. Pathological changes in hepatic sinusoidal endothelial cells in Schistosoma japonicum-infected mice[J]. Trop Med Infect Dis, 2023, 8(2): 124.
[20]	So RJ, Collins SL, Chan-Li Y, et al. Localized knockout of E-cadherin in subglottic mucosa increases fibrosis[J]. Otolaryngol Head Neck Surg, 2025, 172(6): 2003-2008.
[21]	Peng DD, Fu MY, Wang MN, et al. Targeting TGF-β signal transduction for fibrosis and cancer therapy[J]. Mol Cancer, 2022, 21(1): 104.
[22]	Zhang CY, Zhang Y, Hu X, et al. Luteolin inhibits subretinal fibrosis and epithelial-mesenchymal transition in laser-induced mouse model via suppression of Smad2/3 and YAP signaling[J]. Phytomedicine, 2023, 116: 154865.
[23]	Lee JH, Massagué J. TGF-β in developmental and fibrogenic EMTs[J]. Semin Cancer Biol, 2022, 86(Pt 2): 136-145.

基因名称 Gene name	引物序列（5'→3'） Primer sequence (5'→3')
甘油醛-3-磷酸脱氢酶	F: CATCACTGCCACCCAGAAGACTG
GAPDH	R: ATGCCATGAGCTTCCCGTTCAG
E-钙黏蛋白	F: GGTCATCAGTGTGCTCACCTCT
E-cad	R: GCTGTTGTGCTCAAGCCTTCAC
波形蛋白	F: CGGAAAGTGGAATCCTTGCAGG
Vim	R: AGCAGTGAGGTCAGGCTTGGAA
α平滑肌肌动蛋白	F: CTGGTATTGTGCTGGACTCTG
α-SMA	R: GATCTTCATGAGGTAGTCGGT
Ⅰ型胶原蛋白	F: CCTCAGGGTATTGCTGGACAAC
Col-1	R: CAGAAGGACCTTGTTTGCCAGG
Ⅲ型胶原蛋白	F: GACCAAAAGGTGATGCTGGACAG
Col-3	R: CAAGACCTCGTGCTCCAGTTAG