Ferroptosis-centered Disease Response Information
General Information of the Disease (ID: DIS00126)
Name |
Endometriosis
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ICD |
ICD-11: GA10
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Full List of Target(s) of This Ferroptosis-centered Disease
Phospholipid hydroperoxide glutathione peroxidase (GPX4)
In total 3 item(s) under this target | |||||
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target | [1] | ||||
Target for Ferroptosis | Suppressor | ||||
Responsed Disease | Endometriosis [ICD-11: GA10] | ||||
Responsed Drug | Baicalein | Investigative | |||
Pathway Response | Ferroptosis | hsa04216 | |||
Fatty acid metabolism | hsa01212 | ||||
Cell Process | Cell ferroptosis | ||||
In Vitro Model | THP-1 cells | Childhood acute monocytic leukemia | Homo sapiens | CVCL_0006 | |
hMPs (Human macrophages) | |||||
Response regulation | Baicalein, a potential anti-ferroptosis compound, increased GPX4 expression, significantly inhibited ferroptosis, and restored phagocytosis of THP-1 cells in vitro. Collectively, our study reveals that ferroptosis triggered by high iron in cyst fluid promotes the development of endometriosis by impairing macrophage phagocytosis and producing more angiogenic cytokines (e.g., IL8 and VEGFA). | ||||
Experiment 2 Reporting the Ferroptosis-centered Disease Response by This Target | [2] | ||||
Target for Ferroptosis | Suppressor | ||||
Responsed Disease | Endometriosis [ICD-11: GA10] | ||||
Responsed Regulator | ADAMTS9-AS1 (IncRNA) | Suppressor | |||
Pathway Response | Glutathione metabolism | hsa00480 | |||
Fatty acid metabolism | hsa01212 | ||||
Cell Process | Cell ferroptosis | ||||
Cell proliferation | |||||
Cell migration | |||||
In Vitro Model | hEECs (Human esophageal epithelial cells) | ||||
mESCs (Mouse endometrial stromal cells) | |||||
mEESCs (Mouse ectopic endometrial stromal cells) | |||||
In Vivo Model |
Female BALB/c mice (4-6 weeks old, 18-20 g) were obtained from Shanghai Regan Biotechnology Co., Ltd. (Shanghai, China) and were reared in a specific, pathogen-free facility. After 1 week of acclimatization, mice were randomly divided into two groups: the donor group (n = 10) and recipient groups (n = 10). Ovariosteresis and estradiol valerate injection (0.5 ug/mouse/week; Aladdin, Shanghai, China) was carried out to avoid differences in the estrous cycle. Mice were anesthetized by 2% isoflurane, and then the ovaries on both sides were exposed through flank incisions and removed. Donor mice were sacrificed under isoflurane anesthesia, and each uterine horn of the donor mice was concentrated and peeled in warm PBS to remove uterine muscle. Endometrial tissues were weighed and cut into small fragments with scissors and resuspended in sterile PBS with 1 x ampicillin (Beyotime, Shanghai, China). After that, endometrium preparation was intraperitoneally injected into two recipient mice (50 mg/mouse). Two weeks after EM transplantation, endometriosis lesions and eutopic endometrial tissues were removed from the peritoneal cavities and uteri.
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Response regulation | ADAMTS9-AS1 functioned as a competing endogenous RNA (ceRNA) by sponging miR-6516-5p to derepress the expression of GPX4, the critical repressor of ferroptosis. Taken together, these results demonstrate that upregulated ADAMTS9-AS1 accelerates ESC proliferation and migration by regulating miR-6516-5p/GPX4-dependent ferroptosis and may be a potential target for the treatment of Endometriosis. | ||||
Experiment 3 Reporting the Ferroptosis-centered Disease Response by This Target | [2] | ||||
Target for Ferroptosis | Suppressor | ||||
Responsed Disease | Endometriosis [ICD-11: GA10] | ||||
Responsed Regulator | hsa-miR-6516-5p (miRNA) | Driver | |||
Pathway Response | Glutathione metabolism | hsa00480 | |||
Fatty acid metabolism | hsa01212 | ||||
Cell Process | Cell ferroptosis | ||||
Cell proliferation | |||||
Cell migration | |||||
In Vitro Model | hEECs (Human esophageal epithelial cells) | ||||
mESCs (Mouse endometrial stromal cells) | |||||
mEESCs (Mouse ectopic endometrial stromal cells) | |||||
In Vivo Model |
Female BALB/c mice (4-6 weeks old, 18-20 g) were obtained from Shanghai Regan Biotechnology Co., Ltd. (Shanghai, China) and were reared in a specific, pathogen-free facility. After 1 week of acclimatization, mice were randomly divided into two groups: the donor group (n = 10) and recipient groups (n = 10). Ovariosteresis and estradiol valerate injection (0.5 ug/mouse/week; Aladdin, Shanghai, China) was carried out to avoid differences in the estrous cycle. Mice were anesthetized by 2% isoflurane, and then the ovaries on both sides were exposed through flank incisions and removed. Donor mice were sacrificed under isoflurane anesthesia, and each uterine horn of the donor mice was concentrated and peeled in warm PBS to remove uterine muscle. Endometrial tissues were weighed and cut into small fragments with scissors and resuspended in sterile PBS with 1 x ampicillin (Beyotime, Shanghai, China). After that, endometrium preparation was intraperitoneally injected into two recipient mice (50 mg/mouse). Two weeks after EM transplantation, endometriosis lesions and eutopic endometrial tissues were removed from the peritoneal cavities and uteri.
Click to Show/Hide
|
||||
Response regulation | ADAMTS9-AS1 functioned as a competing endogenous RNA (ceRNA) by sponging miR-6516-5p to derepress the expression of GPX4, the critical repressor of ferroptosis. Taken together, these results demonstrate that upregulated ADAMTS9-AS1 accelerates ESC proliferation and migration by regulating miR-6516-5p/GPX4-dependent ferroptosis and may be a potential target for the treatment of Endometriosis. | ||||
Unspecific Target
In total 3 item(s) under this target | |||||
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target | [3] | ||||
Responsed Disease | Endometriosis [ICD-11: GA10] | ||||
Responsed Regulator | MALAT1 (IncRNA) | Suppressor | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Cell Process | Cell ferroptosis | ||||
In Vitro Model | hESCs (Human endometrial stromal cells) | ||||
In Vivo Model |
Seven-to-8-week-old C57BL/6 female mice were obtained and 17-b-estradiol-3-benzoate (30 ug/kg, Sigma) was administered to each mouse every day for 3 days. We removed uterine horns from the donor mice and added them to saline. Endometrium was cut into 1 mm2 fragments. The endometrial fragments from each uterine horn were suspended in 0.3 ml saline and injected into the peritoneal cavities of recipient mice with an 18-gauge needle. At 8 days (5 days after the operation), endometrial-like lesions were established, and they were randomly divided into two groups (each group contained 12 mice). In the experimental group, each mouse received erastin (20 mg/kg/day) by intraperitoneal injection over a 7-day period. In the control group, DMSO was used instead of erastin.
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Response regulation | Knockdown of MALAT1 facilitates erastin-induced ferroptosis by targeting miR-145-5p/MUC1 signaling. The synergistic effect of MALAT1 knockdown and erastin induction in ferroptosis may be a new therapeutic strategy for endometriosis. | ||||
Experiment 2 Reporting the Ferroptosis-centered Disease Response by This Target | [3] | ||||
Responsed Disease | Endometriosis [ICD-11: GA10] | ||||
Responsed Regulator | hsa-miR-145-5p (miRNA) | Driver | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Cell Process | Cell ferroptosis | ||||
In Vitro Model | hESCs (Human endometrial stromal cells) | ||||
In Vivo Model |
Seven-to-8-week-old C57BL/6 female mice were obtained and 17-b-estradiol-3-benzoate (30 ug/kg, Sigma) was administered to each mouse every day for 3 days. We removed uterine horns from the donor mice and added them to saline. Endometrium was cut into 1 mm2 fragments. The endometrial fragments from each uterine horn were suspended in 0.3 ml saline and injected into the peritoneal cavities of recipient mice with an 18-gauge needle. At 8 days (5 days after the operation), endometrial-like lesions were established, and they were randomly divided into two groups (each group contained 12 mice). In the experimental group, each mouse received erastin (20 mg/kg/day) by intraperitoneal injection over a 7-day period. In the control group, DMSO was used instead of erastin.
Click to Show/Hide
|
||||
Response regulation | Knockdown of MALAT1 facilitates erastin-induced ferroptosis by targeting miR-145-5p/MUC1 signaling. The synergistic effect of MALAT1 knockdown and erastin induction in ferroptosis may be a new therapeutic strategy for endometriosis. | ||||
Experiment 3 Reporting the Ferroptosis-centered Disease Response by This Target | [3] | ||||
Responsed Disease | Endometriosis [ICD-11: GA10] | ||||
Responsed Regulator | Mucin-1 (MUC1) | Suppressor | |||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Cell Process | Cell ferroptosis | ||||
In Vitro Model | hESCs (Human endometrial stromal cells) | ||||
In Vivo Model |
Seven-to-8-week-old C57BL/6 female mice were obtained and 17-b-estradiol-3-benzoate (30 ug/kg, Sigma) was administered to each mouse every day for 3 days. We removed uterine horns from the donor mice and added them to saline. Endometrium was cut into 1 mm2 fragments. The endometrial fragments from each uterine horn were suspended in 0.3 ml saline and injected into the peritoneal cavities of recipient mice with an 18-gauge needle. At 8 days (5 days after the operation), endometrial-like lesions were established, and they were randomly divided into two groups (each group contained 12 mice). In the experimental group, each mouse received erastin (20 mg/kg/day) by intraperitoneal injection over a 7-day period. In the control group, DMSO was used instead of erastin.
Click to Show/Hide
|
||||
Response regulation | Knockdown of MALAT1 facilitates erastin-induced ferroptosis by targeting miR-145-5p/ MUC1 signaling. The synergistic effect of MALAT1 knockdown and erastin induction in ferroptosis may be a new therapeutic strategy for endometriosis. | ||||
References