最近的研究表明，TIMP1在不同類型的癌癥中扮演了復(fù)雜的角色。例如，一些研究表明，TIMP1通過抑制MMPs的活性來阻止腫瘤細(xì)胞的遷移和侵襲。但其他研究表明，TIMP1也可能促進(jìn)腫瘤的生長(zhǎng)和轉(zhuǎn)移。此外，TIMP1還被發(fā)現(xiàn)參與了多種疾病的發(fā)展，如心血管疾病、骨質(zhì)疏松癥和關(guān)節(jié)炎等。

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.

1. Study implicated TIMP1, released from the vasculature, as a mediator of the tumorpromoting effects of endothelial PECAM1, thus suggesting its potential role in the progression of metastatic tumors. PMID: 29845213
2. miR-138 and ER stress were induced in osteoporosis and then promoted the apoptosis of osteoblasts, at least in part, through TIMP-1. PMID: 29291636
3. TIMP-1 is upregulated in liver fibrosis and hepatocellular carcinoma, potentially implying diagnostic relevance in the non-invasive assessment of liver fibrosis or in HCC detection6. However, our study in TIMP-1-deficient mice did not confirm a functional role of TIMP-1 in the development of liver fibrosis or hepatocellular carcinoma. PMID: 28386095
4. gingival fibroblasts cell-based therapy is a promising approach to inhibit aneurysm progression and rupture through local production of Timp-1 PMID: 28582477
5. These results show that MMP-9/TIMP-1 system disturbance and changes of histological structure in uteri tissue are involved in fluoride-induced reproductive dysfunctions. PMID: 28064417
6. Tissue inhibitor of matrix metalloproteinases 1 (TIMP1) inhibition resensitized tumors to gemcitabine and radiotherapy. PMID: 28765154
7. proteomic analysis of the mesenchymal stem cells secretome identified the TIMP-1 as a potential effector molecule responsible for the anti-angiogenic properties of MSC PMID: 26898191
8. TIMP1 signaling via CD63 leads to activation of hepatic stellate cells, which create an environment in the liver that increases its susceptibility to pancreatic tumor cells. PMID: 27506299
9. This study highlights a previously undescribed integral role for TIMP1 in both vascular network maturation and adaptations to ischemia or alterations in flow. PMID: 27430487
10. TIMP-1 was identified as a selectively upregulated component secreted from immature astrocytes from human pluripotent stem cells. PMID: 27134175
11. demonstrate that TIMP-2 plays a greater protective role than TIMP-1 during the pathogenesis of atherosclerosis PMID: 26645981
12. Our findings reveal that elevated levels of TIMP-1 impact on neutrophil homeostasis via signaling through CD63. PMID: 26001794
13. TIMP-1 is a ligand of LRP-1 and we highlight a new example of its MMP-independent, cytokine-like functions. PMID: 25075518
14. RAB37 regulates the exocytosis of TIMP1 in a nucleotide-dependent manner to inactivate MMP9 migration axis in vitro and in vivo and to suppress tumor metastasis. PMID: 25183545
15. PDGF-D intensifies fibrogenesis by interfering with the fibrolytic activity of the TIMP-1/MMP-2/MMP-9 system, and PDGF-D signaling is mediated through both PDGF-alpha and -beta receptors. PMID: 25576870
16. Reduced beta(2)GP I plays a role in diabetic mice related to vascular protection, inhibiting vascular lipid deposition, and plaque formation by reducing MMPs/TIMPs expression through down-regulation of the p38MAPK signaling pathway. PMID: 25204377
17. Expansion of stem cells counteracts age-related mammary regression in compound Timp1/Timp3-deficient mice. PMID: 25706237
18. essential promoter of hepatic premetastatic niche formation PMID: 25131778
19. TNF-alpha produced by cholestasis can promote liver fibrosis via TIMP-1 production from hepatic stellate cells. PMID: 23755201
20. These data suggest an MMP-independent role of TIMP-1 in regulating CD4 T cell access into the CNS parenchyma during acute JHMV encephalitis PMID: 24156369
21. miR-21 contributes to renal fibrosis by mediating MMP9/TIMP1 PMID: 23443810
22. Gene expression of Mmp-12 and Mmp-13, and Timp-1 was strongly upregulated at all time points in RD compared with controls. Timp-2, Mmp-2, and Mmp-9 expression was modest. PMID: 24526442
23. TIMP-1 protein was detected in synovium. PMID: 24108368
24. Acute and chronic elevated laminar shear stress act to maintain vessel integrity through increasing TIMP-1 production, and the TGFbeta signaling pathway is essential to maintain TIMP-1 expression during chronic shear stress. PMID: 24471921
25. study provides a unifying molecular mechanism for high angiogenic capacity of TIMP-free proMMP-9 PMID: 24174628
26. These observations showed that Serpine-1 and Tissue inhibitor of metalloprotease type-1 did not impact the number of Staphylococcus aures bacteria accumulating at the site of skin infection. PMID: 23776165
27. Report TIMP-1 induction in aortic smooth muscle during the development of abdominal aortic aneurysms. PMID: 24279124
28. This study suggests that miR-17 participates in the regulation of cardiac matrix remodeling and provides a novel therapeutic approach using miR-17 inhibitors to prevent remodeling and heart failure after MI. PMID: 23825222
29. These results not only indicate that TIMP-1 is conducive to HSPC homing; they also identify CD63 and beta1-integrin as a TIMP-1 receptor complex on HSPCs. PMID: 23660069
30. Tpl2 is an important signal transducer for TLR activation of gene expression in Kupffer and stellate cells by the ERK pathway and that suppression of its catalytic activity may be a route toward suppressing fibrosis caused by hepatocellular injuries. PMID: 23080298
31. Spread of Lewis lung carcinoma cells from serum to the lungs was associated with increased serum content of TIMP-1 and TIMP-2. PMID: 23113307
32. Results show enhanced expression and widespread distribution of MMP-2, MMP-9 and their tissue inhibitors TIMP-1 and TIMP-2 in thymus from infected animals. PMID: 23089194
33. Inhibition of MMPs by TIMP-1-overexpression results in decreased plaque progression, increased stabilization and decreased plaque rupture complications in murine vein grafts. PMID: 23071737
34. NO. Our data support the hypothesis that reduced NO levels leads to the dysregulation of plaque clearance by decreasing the MMP-9/TIMP-1 ratio PMID: 23016931
35. We demonstrate that ATP, acting through the P2X7 receptor, induces release of cathepsin B into the extracellular space where it degrades TIMP-1, permitting the MMP-9-dependent migration of glial cells. PMID: 23017058
36. presence of the MMP-9/TIMP-1 heterodimers and the activated MMP-9 enzyme in the injured sciatic nerve within the first 24 h post-injury PMID: 22438979
37. Results support the use of MMP-9 and TIMP-1 as early biomarkers for the presence and extent of perinatal brain injury in human term newborns. PMID: 22289852
38. Results suggest the possible application of IKK2 and Timp-1 inhibitors in treating lung cancer. PMID: 22327365
39. Results show that microglia play a central role in regulating glial cell expression of TIMP-1 and -2, and identify microglial IL-1beta as playing a key role in mediating microglial-astrocyte communication. PMID: 21631912
40. Overexpression of intracellular tissue inhibitor of metalloproteinase 1 stimulated fibroblast proliferation in a matrix metalloproteinase independent manner by activating the p-Akt pathway and related cell cycle progression PMID: 21350939
41. TIMP1 is a negative regulator of adipogenesis. TIMP1 leads to enlarged adipocytes in the state of overnutrition. PMID: 21437772
42. A role for TIMP-1 in regulating HSC function, suggesting a novel mechanism presiding over stem cell quiescence in the framework of the bone marrow milieu. PMID: 21521782
43. Both MMP-9 and TIMP-1 are highly expressed in Lewis lung cancer, and are correlated to tumor invasion and metastasis. PMID: 19624892
44. IL-10, through regulation of the balance between MMPs and TIMP-1, suppresses the foreign body reaction against implanted biomaterials. PMID: 20661871
45. these findings describe a previously uncharacterized role for TIMP-1 in the regulation of oligodendrocytes and astrocytes during development and provide a novel function for TIMP-1 on myelination in the developing CNS. PMID: 21508247
46. Elevated levels of TIMP-1 in the microenvironment of tumour cells can promote metastasis by inducing HIF-1alpha-dependent HGF-signaling. PMID: 21053058
47. Data demonstrate that long-term CNS expression of TIMP1 with complete suppression of gelatinolytic activity does not interfere with physiological brain function. PMID: 20558576
48. Data show that leptin regulates MMP-2 and TIMP-1 activity, and collagen synthesis via p38 MAPK in mouse cardiomyocytes. PMID: 20683677
49. These results indicate that type 1 diabetes can be prevented by TRAIL overexpression through enhancement of TIMP-1 function. PMID: 21047948
50. Data show that wild-type mice had significantly higher levels of SOCS-3 and significantly lower levels of TIMP-1 mRNA and protein than did adiponectin KO mice exposed to both CCl(4) and leptin. PMID: 20564215

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Secreted.

Protease inhibitor I35 (TIMP) family

Found in fetal and adult tissues. Highest levels are found in bone. Also found in lung, ovary and uterus.

KEGG: mmu:21857

STRING: 10090.ENSMUSP00000009530

UniGene: Mm.8245