Schistosoma japonicum protein SjP40 inhibits TGF-β1-induced activation of hepatic stellate cells

Sun, Xiaolei; Zhang, Lingbo; Wang, Jianxin; Chen, Jinling; Zhu, Dandan; Shen, Pei; He, Xue; Pan, Jing; Peng, Wenxia; Duan, Yinong

doi:10.1007/s00436-015-4663-0

Cited by 25 publications

(51 citation statements)

References 33 publications

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“…We have expressed and purified Sjp40, which has been used for stimulation of LX-2 cells in vitro . Results have confirmed that Sjp40 inhibits TGF-β1-induced activation of HSCs in vitro 19 .…”

Section: Introductionsupporting

confidence: 54%

Egg antigen p40 of Schistosoma japonicum promotes senescence in activated hepatic stellate cells via SKP2/P27 signaling pathway

Chen

Zhu

et al. 2017

Sci Rep

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Schistosomiasis is characterized by egg deposition, granulomatous inflammatory reaction and then subsequent hepatic fibrosis formation. Activated HSCs are regarded as the main effector cells in the progression of liver fibrosis and induction of senescence in hepatic stellate cells (HSCs) is vital to the reversion of hepatic fibrosis. Our previous work has showed that S. japonicum egg antigen p40 (Sjp40) could promote HSCs senescence via a STAT3/p53/p21 mechanism. In this paper, the major aim was to explore whether there are other signaling pathways in the process of Sjp40-induced HSCs aging and the underlying effect of SKP2/P27 signal pathway in this procedure. We observed the Sjp40-induced decrease of α-SMA and the senescence of LX-2 cells, and Sjp40 could upregulate P27 and downregulate the protein level of SKP2. The senescence induced by Sjp40 might be reversed in LX-2 cells that treated with P27-specific siRNA or with SKP2-special over-expression plasmid. In addition, we also demonstrated that the decreased expression of P-Rb and α-SMA induced by Sjp40 were partly restored by SKP2-overexpression. These data suggest that Sjp40 might inhibit HSCs activation by promoting cellular senescence via SKP2/P27 signaling pathway, which put forward novel mechanism in the treatment of liver fibrosis.

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Section: Introductionsupporting

confidence: 54%

Egg antigen p40 of Schistosoma japonicum promotes senescence in activated hepatic stellate cells via SKP2/P27 signaling pathway

Chen

Zhu

et al. 2017

Sci Rep

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“…Nevertheless, it has been found recently that schistosome eggs downregulated the expression levels of α-SMA and COL1A1 in activated HSCs to prevent fibrosis (Anthony et al 2010(Anthony et al , 2013. SEA was reported to engage in anti-fibrotic activity by inhibiting HSC activation and inducing HSC apoptosis Sun et al 2015). rSjP40, which is a major component of schistosome eggs, also attenuated TGF-β1-induced HSC activation in vitro Sun et al 2015).…”

Section: Discussionmentioning

confidence: 99%

“…SEA was reported to engage in anti-fibrotic activity by inhibiting HSC activation and inducing HSC apoptosis Sun et al 2015). rSjP40, which is a major component of schistosome eggs, also attenuated TGF-β1-induced HSC activation in vitro Sun et al 2015). However, no study was focused on the direct effect of other schistosome components on activated HSCs.…”

Section: Discussionmentioning

confidence: 99%

“…Hence, Smad4 can be considered as a target for controlling HSC activation during hepatic fibrosis. Previous studies have demonstrated that some schistosome components exhibited an anti-fibrogenic activity on TGF-β1-activated HSCs (Anthony et al 2010(Anthony et al , 2012Duan et al 2014;Sun et al 2015). For example, soluble egg antigens (SEA) from Schistosoma japonicum suppressed the activation of HSCs through the peroxisome proliferator-activated receptor γ (PPARγ) and TGF-β signal pathway ).…”

Section: Introductionmentioning

confidence: 99%

“…P40, a 40-kDa peptide, is a small heat shock protein of schistosomes with α-crystallins and expresses in cercariae, schistosomulum, adult worm, and eggs of schistosomes (Zhou et al 2010). A study in our lab has shown that the recombinant P40 of S. japonicum (rSjP40) inhibits TGF-β1-induced activation of HSCs through TGF-β1/Smad cascades and the ERK pathway (Sun et al 2015). These features of S. japonicum-derived proteins provide a potential strategy for the therapy of hepatic fibrosis.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Recombinant T2 RNase protein of Schistosoma japonicum inhibits expression of α-SMA in LX-2 cells

et al. 2016

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Recombinant T2 RNase glycoprotein, which showed a certain degree of homology to Omega-1 from Schistosoma mansoni eggs, was expressed in adult worms of Schistosoma japonicum, but not in eggs of S. japonicum. The direct biological role of the recombinant T2 RNase protein in activation of hepatic stellate cells (HSCs) remains unknown. In the present study, the immortalized human HSC line (LX-2 cells) was treated with the recombinant T2 RNase protein at indicated concentrations for various time points in vitro. The expression levels of α-smooth muscle actin (α-SMA) and Smad4 were detected by Western blot. The results showed that the recombinant T2 RNase protein significantly diminished the expression levels of α-SMA and Smad4 in LX-2 cells. The upregulated expression levels of α-SMA and Smad4 by TGF-β1 in LX-2 cells were both suppressed by the recombinant T2 RNase protein. These data suggest that the recombinant T2 RNase protein may be a potential target of therapeutic strategy for the treatment of hepatic fibrosis.

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microRNA‐146a is involved in rSjP40‐inhibited activation of LX‐2 cells by targeting Smad4 expression

Zhu

Zhou

et al. 2018

J of Cellular Biochemistry

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Previous studies have demonstrated that the recombinant Schistosoma japonicum protein P40 (rSjP40) could inhibit activation of hepatic stellate cells (HSCs) through the TGF-β1/Smads signaling pathway. Since multiple microRNAs could play essential roles in HSC activation and in the process of hepatic fibrosis through targeting Smads, we attempted to seek the potential microRNAs that could be involved in rSjP40-induced inhibition of HSC activation. Using the method of quantitative real-time PCR, we found that rSjP40 could induce miR-146a expression in LX-2 cells. The down-regulated expression levels of Smad4 and α-SMA in LX-2 cells induced by rSjP40 were partially restored by an miR-146a inhibitor. miR-146a can be involved in rSjP40-induced inhibition of HSC activation through targeting Smad4. These findings provide us a new idea to explore the potential mechanisms by which rSjP40 could regulate the process of hepatic fibrosis.

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Schistosoma japonicum protein SjP40 inhibits TGF-β1-induced activation of hepatic stellate cells

Cited by 25 publications

References 33 publications

Egg antigen p40 of Schistosoma japonicum promotes senescence in activated hepatic stellate cells via SKP2/P27 signaling pathway

Egg antigen p40 of Schistosoma japonicum promotes senescence in activated hepatic stellate cells via SKP2/P27 signaling pathway

Recombinant T2 RNase protein of Schistosoma japonicum inhibits expression of α-SMA in LX-2 cells

microRNA‐146a is involved in rSjP40‐inhibited activation of LX‐2 cells by targeting Smad4 expression

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