Abstract
Introduction: C-Reactive Protein (CRP) is an important immunomodulatory molecule. Early studies have indicated that CRP is elevated in preeclamptic patient sera, but its function remains unclear. CRP is known to bind with phosphocholine (PC) of bacteria membrane to kill bacteria by triggering innate immune response. Phosphocholination is a post-translational modification mediated by PC transferase, an enzyme reported expressed only in two tissues, including placenta and testis. Recent studies identified that Neurokinin B (NKB), a known, placenta-enriched pathogenic molecule for preeclampsia (PE), is phosphocholinated. This modification increases its stability, preferentially activates NK3 receptor (NK3R) and promotes PE features. Given CRP can bind to PC on bacterial membranes, the role that phosphocholination plays is a mystery. In light of NKB, being phosphocholinated in the endoplasmic reticulum and signals via the NK3R in the pathogenesis of PE, we feel that elevated CRP may be associated with NKB and contributes to the pathophysiology of PE via NK3R activation. Results: ELISA results show that CRP is significantly elevated in PE vs. control sera_65 ug/mL vs. 10 ug/ml; p<0.0001. Western blot analysis reveals that CRP, NKB, and NK3R are significantly increased in PE vs. control placental tissue. Immunohistochemistry studies indicate that all of these three molecules are abundant in syncytiotrophoblast cells. Co-immunoprecipitation demonstrates an interaction between CRP and NKB. In vitro , we provide the first evidence that CRP decreased the invasion of trophoblast cells from 0.7 ± 0.06 to 0.06 ± 0.001 invasion index; p<0.005, while treatment with SB222200 ameliorates shallow invasion from 0.28 ± 0.09 to 0.55 ± 0.07 invasion index; p<0.05. Significantly, infusion of CRP into pregnant mice induces hypertension (169.152 ± 14.7 mmHg vs. 141.916 ± 6.93 mmHg; p<0.05) and proteinuria (28.78 ± 13.56 mg albumin/μg Cr vs. 13.87 ± 3.277 mg albumin/μg Cr; p<0.05). Conclusion: Our findings demonstrate elevated CRP contributes to PE and NKB/NK3R is a new mechanism underlying CRP-mediated shallow invasion and disease development. These studies suggest novel pathogenic biomarkers and innovative therapies for PE.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.