Ferroptosis Regulator Information

General Information of the Ferroptosis Regulator (ID: REG10055)
Regulator Name Metalloproteinase inhibitor 1 (TIMP1)
Synonyms
CLGI, TIMP; Erythroid-potentiating activity; Fibroblast collagenase inhibitor; Tissue inhibitor of metalloproteinases 1
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Gene Name TIMP1
Gene ID 7076
Regulator Type Protein coding
Uniprot ID P01033
Sequence
MAPFEPLASGILLLLWLIAPSRACTCVPPHPQTAFCNSDLVIRAKFVGTPEVNQTTLYQR
YEIKMTKMYKGFQALGDAADIRFVYTPAMESVCGYFHRSHNRSEEFLIAGKLQDGLLHIT
TCSFVAPWNSLSLAQRRGFTKTYTVGCEECTVFPCLSIPCKLQSGTHCLWTDQLLQGSEK
GFQSRHLACLPREPGLCTWQSLRSQIA

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Family Protease inhibitor I35 (TIMP) family
Function
Metalloproteinase inhibitor that functions by forming one to one complexes with target metalloproteinases, such as collagenases, and irreversibly inactivates them by binding to their catalytic zinc cofactor. Acts on MMP1, MMP2, MMP3, MMP7, MMP8, MMP9, MMP10, MMP11, MMP12, MMP13 and MMP16. Does not act on MMP14. Also functions as a growth factor that regulates cell differentiation, migration and cell death and activates cellular signaling cascades via CD63 and ITGB1. Plays a role in integrin signaling. Mediates erythropoiesis in vitro; but, unlike IL3, it is species-specific, stimulating the growth and differentiation of only human and murine erythroid progenitors.

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HGNC ID
HGNC:11820
KEGG ID hsa:7076
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
TIMP1 can regulate the following target(s), and cause disease/drug response(s). You can browse detail information of target(s) or disease/drug response(s).
Browse Target
Browse Disease
Transferrin receptor protein 1 (TFRC) [Driver; Suppressor; Marker]
 Target Info 
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [1]
Target for Ferroptosis Driver
Responsed Disease Cardiac hypertrophy ICD-11: BC45
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Cell Process Cell ferroptosis
In Vitro Model
 hNCs (Neutrophils cells)
In Vivo Model
The rats were randomly divided into five groups as follows: (1) sham group: the rats underwent sham operation and received vehicle (PBS, caudal vein injection). (2) Model group: the rats were subjected to AAC and received vehicle (PBS, caudal vein injection). (3-5) The treatment groups: the rats were subjected to AAC and after 24 h treated with si-AAB, si-AAB + MSN, or NM + si-AAB + MSN (50 nM siRNA dose per rat every 2 days for 4 weeks, caudal vein injection).

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Response regulation LncRNA AAB was upregulated in the hearts of cardiac hypertrophy rats as well as in the Ang II-induced CMECs. Importantly, we found that lncRNA AAB sponged and sequestered miR-30b-5p to induce the imbalance of MMP9/ TIMP1, which enhanced the activation of transferrin receptor 1 (TFR-1) and then eventually led to the ferroptosis of CMECs.
Phospholipid hydroperoxide glutathione peroxidase (GPX4) [Suppressor]
 Target Info 
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [2]
Target for Ferroptosis Suppressor
Responsed Disease Colorectal cancer ICD-11: 2B91
 Disease Info 
Pathway Response Ferroptosis hsa04216
PI3K-Akt signaling pathway hsa04151
Cell Process Cell ferroptosis
In Vitro Model
 HCT-8 cells Ileocecal adenocarcinoma Homo sapiens CVCL_2478
Response regulation TIMP1 depletion in colorectal cancer cells enhances sorafenib-triggered ferroptosis by reducing PI3K/Akt axis signal transduction. TIMP1 knockdown repressed the activation of the PI3K/Akt pathway and reduced levels of glutathione peroxidase 4 (GPX4), enhancing sorafenib-induced ferroptosis.
Colorectal cancer [ICD-11: 2B91]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [2]
Target Regulator Metalloproteinase inhibitor 1 (TIMP1) Protein coding
 Regulator Info 
Pathway Response Ferroptosis hsa04216
PI3K-Akt signaling pathway hsa04151
Cell Process Cell ferroptosis
In Vitro Model
 HCT-8 cells Ileocecal adenocarcinoma Homo sapiens CVCL_2478
Response regulation TIMP1 depletion in colorectal cancer cells enhances sorafenib-triggered ferroptosis by reducing PI3K/Akt axis signal transduction. TIMP1 knockdown repressed the activation of the PI3K/Akt pathway and reduced levels of glutathione peroxidase 4 (GPX4), enhancing sorafenib-induced ferroptosis.
Cardiac hypertrophy [ICD-11: BC45]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Metalloproteinase inhibitor 1 (TIMP1) Protein coding
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Cell Process Cell ferroptosis
In Vitro Model
 hNCs (Neutrophils cells)
In Vivo Model
The rats were randomly divided into five groups as follows: (1) sham group: the rats underwent sham operation and received vehicle (PBS, caudal vein injection). (2) Model group: the rats were subjected to AAC and received vehicle (PBS, caudal vein injection). (3-5) The treatment groups: the rats were subjected to AAC and after 24 h treated with si-AAB, si-AAB + MSN, or NM + si-AAB + MSN (50 nM siRNA dose per rat every 2 days for 4 weeks, caudal vein injection).

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Response regulation LncRNA AAB was upregulated in the hearts of cardiac hypertrophy rats as well as in the Ang II-induced CMECs. Importantly, we found that lncRNA AAB sponged and sequestered miR-30b-5p to induce the imbalance of MMP9/ TIMP1, which enhanced the activation of transferrin receptor 1 (TFR-1) and then eventually led to the ferroptosis of CMECs.
References
Ref 1 Neutrophil-like cell membrane-coated siRNA of lncRNA AABR07017145.1 therapy for cardiac hypertrophy via inhibiting ferroptosis of CMECs. Mol Ther Nucleic Acids. 2021 Nov 3;27:16-36. doi: 10.1016/j.omtn.2021.10.024. eCollection 2022 Mar 8.
Ref 2 TIMP1 represses sorafenib-triggered ferroptosis in colorectal cancer cells by activating the PI3K/Akt signaling pathway. Immunopharmacol Immunotoxicol. 2023 Dec;45(4):419-425. doi: 10.1080/08923973.2022.2160731. Epub 2023 Mar 12.