General Information of the Disease (ID: DIS00137)
Name
Preeclampsia
ICD
ICD-11: JA24
Full List of Target(s) of This Ferroptosis-centered Disease
Solute carrier family 40 member 1 (SLC40A1)
In total 2 item(s) under this target
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target [1]
Target for Ferroptosis Suppressor
Responsed Disease Preeclampsia [ICD-11: 2F37.Y]
Responsed Regulator hsa-miR-30b-5p (miRNA) Driver
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model HTR-8/SVneo cells Normal Homo sapiens CVCL_7162
hETCs (Human first-trimester extravillous trophoblast cells)
In Vivo Model
Pregnant SD rats were randomly dived into four groups: sham group (n = 8), PE group (n = 8), PE + ferrostatin-1 group ( n= 8), and PE + miR-30b-5p inhibition group (n = 8). On day 14 of pregnancy, PE rat model was established through reduced uterine perfusion pressure (RUPP) surgery, wherein constrictive silver clips were placed on the aorta (0.203-mm clips) superior to the iliac bifurcation and on the ovarian vessels (0.100-mm clips), according to a previous description. Sham rats were operated on in a fashion similar to that of RUPP rats, but without clipping. Mini-pumps were also intraperitoneally inserted into rats on day 14 of pregnancy. The mini-pump in each rat delivered the ferrostatin-1 at a dose of 10 umol/kg/day for 5 days. An miR-30b-5p antagonist (GenePharma) was injected from the tail veins on day 13 of gestation, at a rate of 100 uL/day for 6 days. The blood pressure was measured on days 14, 16, and 19 of gestation using catheters inserted into the carotid artery and jugular vein.

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Response regulation Abnormally up-regulated miR-30b-5p triggered the ferroptosis in trophoblasts under hypoxic conditions by down-regulating SLC7A11, Pax3, and Pax3-downstream target, FPN1. Blockage of miR-30b-5p up-regulation or direct inhibition of ferroptosis attenuated preeclampsia (PE) symptoms in the rat model, making miR-30b-5p a potential therapeutic target for preeclampsia.
Experiment 2 Reporting the Ferroptosis-centered Disease Response by This Target [1]
Target for Ferroptosis Suppressor
Responsed Disease Preeclampsia [ICD-11: 2F37.Y]
Responsed Regulator Paired box protein Pax-3 (PAX3) Suppressor
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model HTR-8/SVneo cells Normal Homo sapiens CVCL_7162
hETCs (Human first-trimester extravillous trophoblast cells)
In Vivo Model
Pregnant SD rats were randomly dived into four groups: sham group (n = 8), PE group (n = 8), PE + ferrostatin-1 group ( n= 8), and PE + miR-30b-5p inhibition group (n = 8). On day 14 of pregnancy, PE rat model was established through reduced uterine perfusion pressure (RUPP) surgery, wherein constrictive silver clips were placed on the aorta (0.203-mm clips) superior to the iliac bifurcation and on the ovarian vessels (0.100-mm clips), according to a previous description. Sham rats were operated on in a fashion similar to that of RUPP rats, but without clipping. Mini-pumps were also intraperitoneally inserted into rats on day 14 of pregnancy. The mini-pump in each rat delivered the ferrostatin-1 at a dose of 10 umol/kg/day for 5 days. An miR-30b-5p antagonist (GenePharma) was injected from the tail veins on day 13 of gestation, at a rate of 100 uL/day for 6 days. The blood pressure was measured on days 14, 16, and 19 of gestation using catheters inserted into the carotid artery and jugular vein.

    Click to Show/Hide
Response regulation Abnormally up-regulated miR-30b-5p triggered the ferroptosis in trophoblasts under hypoxic conditions by down-regulating SLC7A11, Pax3, and Pax3-downstream target, FPN1. Blockage of miR-30b-5p up-regulation or direct inhibition of ferroptosis attenuated preeclampsia (PE) symptoms in the rat model, making miR-30b-5p a potential therapeutic target for preeclampsia.
Cystine/glutamate transporter (SLC7A11)
In total 3 item(s) under this target
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target [2]
Target for Ferroptosis Suppressor
Responsed Disease Preeclampsia [ICD-11: 2F37.Y]
Responsed Regulator Pannexin-1 (PANX1) Driver
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model hPTs (Human placental tissues)
Response regulation Panx1 and TLR4 are suggested to induce ferroptosis in Preeclampsia via SLC7A11-mediated signaling pathways, offering a novel perspective on PE pathogenesis and novel diagnostic tools for Preeclampsia.
Experiment 2 Reporting the Ferroptosis-centered Disease Response by This Target [1]
Target for Ferroptosis Suppressor
Responsed Disease Preeclampsia [ICD-11: 2F37.Y]
Responsed Regulator hsa-miR-30b-5p (miRNA) Driver
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model HTR-8/SVneo cells Normal Homo sapiens CVCL_7162
hETCs (Human first-trimester extravillous trophoblast cells)
In Vivo Model
Pregnant SD rats were randomly dived into four groups: sham group (n = 8), PE group (n = 8), PE + ferrostatin-1 group ( n= 8), and PE + miR-30b-5p inhibition group (n = 8). On day 14 of pregnancy, PE rat model was established through reduced uterine perfusion pressure (RUPP) surgery, wherein constrictive silver clips were placed on the aorta (0.203-mm clips) superior to the iliac bifurcation and on the ovarian vessels (0.100-mm clips), according to a previous description. Sham rats were operated on in a fashion similar to that of RUPP rats, but without clipping. Mini-pumps were also intraperitoneally inserted into rats on day 14 of pregnancy. The mini-pump in each rat delivered the ferrostatin-1 at a dose of 10 umol/kg/day for 5 days. An miR-30b-5p antagonist (GenePharma) was injected from the tail veins on day 13 of gestation, at a rate of 100 uL/day for 6 days. The blood pressure was measured on days 14, 16, and 19 of gestation using catheters inserted into the carotid artery and jugular vein.

    Click to Show/Hide
Response regulation Abnormally up-regulated miR-30b-5p triggered the ferroptosis in trophoblasts under hypoxic conditions by down-regulating SLC7A11, Pax3, and Pax3-downstream target, FPN1. Blockage of miR-30b-5p up-regulation or direct inhibition of ferroptosis attenuated preeclampsia (PE) symptoms in the rat model, making miR-30b-5p a potential therapeutic target for preeclampsia.
Experiment 3 Reporting the Ferroptosis-centered Disease Response by This Target [2]
Target for Ferroptosis Suppressor
Responsed Disease Preeclampsia [ICD-11: 2F37.Y]
Responsed Regulator Toll-like receptor 4 (TLR4) Driver
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model hPTs (Human placental tissues)
Response regulation Panx1 and TLR4 are suggested to induce ferroptosis in Preeclampsia via SLC7A11-mediated signaling pathways, offering a novel perspective on PE pathogenesis and novel diagnostic tools for Preeclampsia.
Aspartate aminotransferase, cytoplasmic (GOT1)
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target [3]
Target for Ferroptosis Driver
Responsed Disease Preeclampsia [ICD-11: 2F37.Y]
Responsed Regulator hsa-miR-2115-3p (miRNA) Suppressor
Pathway Response Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model HTR-8/SVneo cells Normal Homo sapiens CVCL_7162
In Vivo Model
Pregnant rats were randomly divided into 3 groups on gestational day 13, with 8 in each group: Sham group, PE group, and PE + ferrostatin-1 (FI) group. As previously mentioned, on gestational day 14, rats in the PE and PE + FI groups were subjected to reduced uterine perfusion pressure (RUPP) surgery to establish the PE model. Briefly, pregnant rats were anesthetized, sterilized with iodophor, and then opened. A contractile silver clip (0.203 mm) was placed on the aorta above the iliac bifurcation, as well as the bilateral uterine arcades at the end of the ovary were reduced with restrictive clips (0.100 mm) to the ovarian collaterals of the uterus. The rats in the Sham group were operated in a manner similar to the RUPP rats but were not clipped. On a gestational day 14, the mini-pumps were also inserted into the rat's peritoneum. The mini-pump in each rat of the PE + FI group was used to deliver FI at a dose of 10 mol/kg/d for 5 d. Systolic and diastolic blood pressure (SBP and DBP) were measured on gestational days 14, 16, and 19 using catheters inserted into the carotid artery and jugular vein. On a gestational day 19, urine, blood, and placenta of rats were collected for subsequent experiments. Urine protein content was detected using a commercial kit (C035-2, Nanjing Jiancheng, China). Plasma sFlt-1 content was detected by a commercial kit (ml059017, Mlbio, China). The remaining samples were stored at -80 .

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Response regulation miR-2115-3p might interact with the GOT1 mRNA to downregulate its expression, further inhibiting the hypoxia-promoted ferroptosis in a preeclampsia model.
References
Ref 1 miR-30-5p-mediated ferroptosis of trophoblasts is implicated in the pathogenesis of preeclampsia. Redox Biol. 2020 Jan;29:101402. doi: 10.1016/j.redox.2019.101402. Epub 2019 Dec 9.
Ref 2 Novel insights into the SLC7A11-mediated ferroptosis signaling pathways in preeclampsia patients: identifying pannexin 1 and toll-like receptor 4 as innovative prospective diagnostic biomarkers. J Assist Reprod Genet. 2022 May;39(5):1115-1124. doi: 10.1007/s10815-022-02443-x. Epub 2022 Mar 24.
Ref 3 miR-2115-3p inhibits ferroptosis by downregulating the expression of glutamic-oxaloacetic transaminase in preeclampsia. Placenta. 2022 Nov;129:94-103. doi: 10.1016/j.placenta.2022.09.014. Epub 2022 Oct 10.