Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.23 (MMP)
 4,246 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The interleukin-6 (IL-6)/Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) pathway mediates cell proliferation and migration. S-phase kinase-associated protein-2 (Skp2) catalyzes the ubiquitylation of p27 and p21. Here we investigated that the cross-talk of the two pathways regulates motility and invasion of gastric cancer SGC7901 and MGC803 cells. Both cell lines endogenously secret IL-6, and blockage of IL-6 or JAK2 inhibited the activation of JAK2 and STAT3. Depletion of STAT3 downregulated Skp2 expression, and thereby increased the expression of p27 and p21. The depletion of STAT3 inhibited the ability of cells to migrate and invade, and impaired the cellular cytoskeleton mainly microtubules; while the depletion of p27 partially restored the impaired ability to migrate, and reversed the impaired microfilaments, further inhibited the ability to invade, but had little effect on microtubules and cellular adhering ability of STAT3-depleted cells. STAT3 depletion inhibited the activity of RhoA and the interaction with stathmin, downregulated the expression of pFAK (phosphorylated focal adhesion kinase), acetylated-tubulin, RECK (reversion-inducing-cysteine-rich protein with kazal motifs) and Sp1, upregulated E-cadherin, and reduced the activities of MMP (matrix metalloproteinase)-2 and -9. The depletion of p27 increased RhoA (Ras homolog family member A) activity, upregulated RECK, and downregulated E-cadherin and Sp1 in STAT3-depleted cells. The results indicate that the interaction between STAT3 and Skp2/p27/p21 pathway plays an important role in mediating the motility, migration and invasion of gastric cancer cells, and inhibition of STAT3 may be a useful therapeutic approach for metastasis of gastric cancer, but caution needs to be taken for its effects on Skp2/p27/p21 pathway.
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PMID:STAT3 interacts with Skp2/p27/p21 pathway to regulate the motility and invasion of gastric cancer cells. 2333 63

Most patients with chronic kidney disease (CKD) present with proteinuria and extracellular matrix (ECM) deposition in the interstitium. Matrix metalloproteinase-2 (MMP-2) is important for maintaining ECM metabolism and it affects the formation and development of CKD. Autophagy has been reported to be protective against renal tubular injury, but the role of autophagy related to ECM metabolism is unclear. Rab7 is a shared molecule of endocytosis and autophagy. The aim of this study is to explore the role of autophagy in regulating MMP-2 activity and to determine whether Rab7 functions in regulating MMP-2 activity and injury in albumin-overloaded TECs. In this study, abovine serum albumin (BSA)-overload rat model was first established and collagen deposition and deficient autophagic response were observed in vivo, and stimulation with albumin nanoparticles resulted in MMP-2 overactivation and obstructed autophagic flux induced by lysosomal dysfunction in vitro. Furthermore, overactivation of MMP-2 was mediated by its related regulatory molecules such as membrane-type 1 MMP (MT1-MMP), tissue inhibitor of metalloproteinase-2 (TIMP-2) and reversion-inducing-cysteine-rich protein with kazal motifs (RECK) on the membrane of TECs (HK-2 cellline). After up-regulating Rab7, albumin-induced MMP-2 overactivation was attenuated, which was reversed by chloroquine (CQ; an endocytosis inhibitor). In addition, our data indicated that up-regulation of Rab7 relieved epithelial-mesenchymal transition (EMT) and apoptosis in albumin-treated TECs. Taken together, our study demonstrated that autophagy regulates MMP-2 activity in a Rab7-dependent manner. Thus, Rab7 is a newly developed target for protecting TECs from albumin-induced injury.
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PMID:Rab7 empowers renal tubular epithelial cells with autophagy-mediated protection against albumin-induced injury. 2993 81