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)

Extracellular matrix (ECM) remodeling is the hallmark of hypertensive nephropathy. Uncontrolled proteolytic activity due to an imbalance between matrix metalloproteinases and tissue inhibitors of metalloproteinases (MMPs/TIMPs) has been implicated in renovascular fibrosis. We hypothesized that inhibition of MMPs will reduce excess ECM deposition and modulate autophagy to attenuate hypertension. Dahl-salt sensitive (Dahl/SS) and Lewis rats were fed on high salt diet and treated without or with 1.2 mg/kg b.w. of GM6001 (MMP inhibitor) by intra-peritoneal injection on alternate days for 4 weeks. Blood pressure, renal cortical blood flow, vascular density, collagen, elastin and MMPs/TIMPs were measured. GM6001 treatment significantly reduced mean blood pressure in hypertensive Dahl/SS rats. Renal resistive index was increased in hypertensive Dahl/SS rats and Doppler flowmetry showed reduced cortical perfusion. Barium angiography demonstrated a reduction in terminal branches of renal vasculature. Inhibition of MMPs by GM6001 resulted in a significant improvement in all the parameters including renal function. In hypertensive Dahl/SS rats, protein levels of MMP-9, -2 and -13 were increased including the activity of MMP-9 and -2; TIMP-1 and -2 levels were increased whereas, TIMP-3 levels were similar to Lewis controls. Administration of GM6001 reduced the activity of MMPs and increased the levels of TIMP-1, -2 and -3. MMP inhibition reduced type -1 collagen deposition and increased elastin in the intra-renal vessels indicating reduced fibrosis. Autophagy markers were decreased in hypertensive Dahl/SS rats and GM6001 treatment enhanced their levels. We conclude that MMP inhibition (GM6001) reduces adverse renovascular remodeling in hypertension by modulating ECM turnover and stimulating autophagy.
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PMID:Matrix Metalloproteinase Inhibition Mitigates Renovascular Remodeling in Salt-Sensitive Hypertension. 2415 76

MicroRNAs (miRNAs) are critical regulators in organ development. Among them, miR-191 is known to be regulated in early embryogenesis and dysregulated in cancer. This role in undifferentiated tissues suggests a possible part of miR-191 also in bone marrow derived mesenchymal stem cells (BMSCs) physiology. Here, we report that miR-191 decreased MMP expression and migration of BMSCs. Conditioned media of miR-191 overexpressing BMSCs block VEGF expression, and inhibit angiogenesis of HUVECs. Under osteogenic culture conditions, inhibition of miR-191 significantly induces bone formation. Moreover, our studies showed miR-191 might influence chondrogenesis of BMSCs by directly targeting CCAAT Enhancer Binding Protein Beta (CEBPB). Taken together, here we demonstrate the role of miR-191 in differentiation, migration and paracrine function of BMSCs.
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PMID:MicroRNA-191 regulates differentiation and migration of mesenchymal stem cells and their paracrine effect on angiogenesis. 3243 19