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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Nature Portfolio
2025-05-01
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| author | Yan An Chenyuan Cao Shaosong Sun Hongli Wu Jinzhi Zhang Rui Li Yakun Zhao |
| author_facet | Yan An Chenyuan Cao Shaosong Sun Hongli Wu Jinzhi Zhang Rui Li Yakun Zhao |
| author_sort | Yan An |
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| description | 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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| spelling | doaj-art-eefd6ec4f6b146f49cbc70ed47ddc1a12025-08-20T01:49:44ZengNature PortfolioScientific Reports2045-23222025-05-0115111110.1038/s41598-025-00164-6SHP1 and its downstream p38/SP1/PI3K/YAP/Notch-1 signaling in trophoblast cells suppressed the progression of Preeclampsia via inhibiting proliferation of SMCsYan An0Chenyuan Cao1Shaosong Sun2Hongli Wu3Jinzhi Zhang4Rui Li5Yakun Zhao6Department of Obstetrics, Affiliated Hospital of Hebei UniversityDepartment of Obstetrics, Affiliated Hospital of Hebei UniversityDepartment of Orthopaedics, Affiliated Hospital of Hebei UniversityDepartment of Obstetrics, Affiliated Hospital of Hebei UniversityDepartment of Obstetrics, Affiliated Hospital of Hebei UniversityDepartment of Obstetrics, Affiliated Hospital of Hebei UniversityDepartment of Obstetrics, Affiliated Hospital of Hebei UniversityAbstract 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.https://doi.org/10.1038/s41598-025-00164-6Shp1Preclampsiap38SP1PI3KYAP |
| spellingShingle | Yan An Chenyuan Cao Shaosong Sun Hongli Wu Jinzhi Zhang Rui Li Yakun Zhao SHP1 and its downstream p38/SP1/PI3K/YAP/Notch-1 signaling in trophoblast cells suppressed the progression of Preeclampsia via inhibiting proliferation of SMCs Scientific Reports Shp1 Preclampsia p38 SP1 PI3K YAP |
| title | SHP1 and its downstream p38/SP1/PI3K/YAP/Notch-1 signaling in trophoblast cells suppressed the progression of Preeclampsia via inhibiting proliferation of SMCs |
| title_full | SHP1 and its downstream p38/SP1/PI3K/YAP/Notch-1 signaling in trophoblast cells suppressed the progression of Preeclampsia via inhibiting proliferation of SMCs |
| title_fullStr | SHP1 and its downstream p38/SP1/PI3K/YAP/Notch-1 signaling in trophoblast cells suppressed the progression of Preeclampsia via inhibiting proliferation of SMCs |
| title_full_unstemmed | SHP1 and its downstream p38/SP1/PI3K/YAP/Notch-1 signaling in trophoblast cells suppressed the progression of Preeclampsia via inhibiting proliferation of SMCs |
| title_short | SHP1 and its downstream p38/SP1/PI3K/YAP/Notch-1 signaling in trophoblast cells suppressed the progression of Preeclampsia via inhibiting proliferation of SMCs |
| title_sort | shp1 and its downstream p38 sp1 pi3k yap notch 1 signaling in trophoblast cells suppressed the progression of preeclampsia via inhibiting proliferation of smcs |
| topic | Shp1 Preclampsia p38 SP1 PI3K YAP |
| url | https://doi.org/10.1038/s41598-025-00164-6 |
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