SHP1 and its downstream p38/SP1/PI3K/YAP/Notch-1 signaling in trophoblast cells suppressed the progression of Preeclampsia via inhibiting proliferation of SMCs
Abstract Preeclampsia leads to high fetal morbidity and pregnancy-induced mortality. However, the detailed molecular pathology of PE is currently unknown. shp1 has been shown to be critical to the pathogenesis of several diseases, but their role in PE requires further validation. In this study, TPI-...
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| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-05-01
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| Series: | Scientific Reports |
| Subjects: | |
| Online Access: | https://doi.org/10.1038/s41598-025-00164-6 |
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| Summary: | Abstract Preeclampsia leads to high fetal morbidity and pregnancy-induced mortality. However, the detailed molecular pathology of PE is currently unknown. shp1 has been shown to be critical to the pathogenesis of several diseases, but their role in PE requires further validation. In this study, TPI-1 administration significantly worsened PE mice resulting in impaired spiral artery remodelling. According to Western blot results, TPI-1 administration down-regulated the protein expression of SHP1 and up-regulated the protein expression of p-P38, p-Src. YAP, SP1, and JAG-1 in PE mice. In addition, Shp1 OE promoted Shp1 and p-Shp1 expression and inhibited SMCs cellular NICD, c-Myc, CyclinD1, MMP- through inhibition of trophoblast p-P38, SP1, PI3K, YAP, JAG1 protein expression as determined by in vitro trophoblast cell lines and smooth muscle cells cultured with trophoblast cell serum. 9, MMP-2 expression inhibited the proliferation and migration of SMCs cells. The P38 activator metformin Hcl inhibited the action of Shp1 OE. The SP1 activator plicamycin inhibited the action of metformin hydrochloride. The PI3K activator 740 Y-P inhibited the action of SP1 activator. The YAP inhibitor CA3 (CIL56) inhibited the action of the action of SP1 activators. In summary, SHP1 affects preeclampsia by inhibiting the expression of P38/SP1/PI3K/YAPxd proteins in trophoblast cells, which in turn regulates the protein expression of NICD, c-Myc, CyclinD1, MMP-9, MMP-2 in SMCs cells. |
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| ISSN: | 2045-2322 |