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

Abstract

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.

Qualitative and quantitative proteomic analyses of Schistosoma japonicum eggs and egg-derived secretory-excretory proteins

“…Schistosomiasis is a chronic parasitic disease affecting more than 250 million people in tropical and subtropical countries [1, 2]. Eggs of the three main Schistosoma species ( Schistosoma mansoni , S. haematobium and S. japonicum ) have been demonstrated to play a major role in human disease attributable to schistosomiasis, being involved in its morbidity, pathology, host immune modulation, diagnosis and transmission [3, 4]. A single female S. japonicum lays approximately 1000 eggs per day inside the veins of its mammal host [5].…”

Long non‐coding RNA RP11‐820 promotes extracellular matrix production via regulating miR‐3178/MYOD1 in human trabecular meshwork cells

“…In this study, we found a combined effect of MYOD1 and STAT3 on accelerating fibronectin and collagen I production. Indeed, the involvement of STAT3 in ECM production was confirmed in renal and liver fibrosis . Therefore, more studies are needed to clarify regulatory mechanisms between MYOD1 and STAT3 in HTMCs.…”

High S phase kinase‑associated protein 2 expression is a potential prognostic biomarker for glioma

“…As an important cell cycle regulating protein, p-Rb serves pivotal roles in tumorigenesis (24). Xu et al (40) used egg antigen p40 of schistosoma japonicum (Sjp40) to trigger the expression of p27 in LX-2 cells and observed that both SKP2 and p-Rb were downregulated. Overexpression of SKP2 reversed p27 protein levels and partially reversed the inhibition of p-Rb expression in Sjp40 treated LX2 cells (40).…”

“…Xu et al (40) used egg antigen p40 of schistosoma japonicum (Sjp40) to trigger the expression of p27 in LX-2 cells and observed that both SKP2 and p-Rb were downregulated. Overexpression of SKP2 reversed p27 protein levels and partially reversed the inhibition of p-Rb expression in Sjp40 treated LX2 cells (40). In the present study, consistent alteration of SKP2 with p-Rb was observed in glioma tissues.…”