ATF3 is involved in rSjP40-mediated inhibition of HSCs activation in Schistosoma japonicum-infected mice.

Publisher: Wiley-Blackwell Country of Publication: England NLM ID: 101083777 Publication Model: Print Cited Medium: Internet ISSN: 1582-4934 (Electronic) Linking ISSN: 15821838 NLM ISO Abbreviation: J Cell Mol Med Subsets: MEDLINE

Publication: Oxford, England : Wiley-Blackwell
Original Publication: Bucharest : "Carol Davila" University Press, 2000-

Activating Transcription Factor 3*/metabolism ; Activating Transcription Factor 3*/genetics ; Hepatic Stellate Cells*/metabolism ; Hepatic Stellate Cells*/parasitology ; Schistosomiasis japonica*/parasitology ; Schistosomiasis japonica*/metabolism ; Schistosomiasis japonica*/genetics ; Schistosoma japonicum* ; Liver Cirrhosis*/parasitology ; Liver Cirrhosis*/genetics ; Liver Cirrhosis*/pathology ; Liver Cirrhosis*/metabolism ; MicroRNAs*/genetics ; MicroRNAs*/metabolism ; Helminth Proteins*/genetics ; Helminth Proteins*/metabolism; Animals ; Mice ; Humans ; Actins/metabolism ; Actins/genetics ; Cell Line ; Gene Expression Regulation ; Liver/metabolism ; Liver/parasitology ; Liver/pathology ; Disease Models, Animal ; Antigens, Helminth

Schistosomiasis is a parasitic disease characterized by liver fibrosis, a process driven by the activation of hepatic stellate cells (HSCs) and subsequent collagen production. Previous studies from our laboratory have demonstrated the ability of Schistosoma japonicum protein P40 (SjP40) to inhibit HSCs activation and exert an antifibrotic effect. In this study, we aimed to elucidate the molecular mechanism underlying the inhibitory effect of recombinant SjP40 (rSjP40) on HSCs activation. Using a cell model in which rSjP40 inhibited LX-2 cell activation, we performed RNA-seq analyses and identified ATF3 as the most significantly altered gene. Further investigation revealed that rSjP40 inhibited HSCs activation partly by suppressing ATF3 activation. Knockdown of ATF3 in mouse liver significantly alleviated S. japonicum-induced liver fibrosis. Moreover, our results indicate that ATF3 is a direct target of microRNA-494-3p, a microRNA associated with anti-liver fibrosis effects. rSjP40 was found to downregulate ATF3 expression by upregulating microRNA-494-3p in LX-2 cells. This downregulation led to the inhibition of the expression of liver fibrosis proteins α-SMA and COL1A1, ultimately alleviating liver fibrosis caused by S. japonicum.
(© 2024 The Author(s). Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

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Keywords: Schistosoma japonicum; ATF3; Schistosoma japonicum protein P40; hepatic stellate cell; microRNA‐494‐3p

0 (Activating Transcription Factor 3)
0 (MicroRNAs)
0 (Helminth Proteins)
0 (p40 egg antigen, Schistosoma)
0 (Atf3 protein, mouse)
0 (Actins)
0 (Antigens, Helminth)

Date Created: 20240720 Date Completed: 20240720 Latest Revision: 20241002

20241003

PMC11190947

10.1111/jcmm.18458

39031798