33 research outputs found
CTGF is a central mediator of tissue remodeling and fibrosis and its inhibition can reverse the process of fibrosis
CTGF is a secreted matricellular protein with very complex biology. It has been shown to modulate many signaling pathways leading to cell adhesion and migration, angiogenesis, myofibroblast activation, and extracellular matrix deposition and remodeling, which together lead to tissue remodeling and fibrosis. It has been reported in the literature that inhibition of CTGF expression by siRNA prevents CCl4-induced liver fibrosis and can reverse fibrosis when administered after significant collagen deposition is observed. A monoclonal antibody to CTGF that is currently in clinical development (FG-3019) has demonstrated the ability to reverse vascular stiffening and improve cardiac function in a rat model of diabetic complications. FG-3019 has also exhibited activity in a murine radiation-induced pulmonary fibrosis model. When FG-3019 was administered to mice after a significant radiation-induced increase in lung density could be observed by CT imaging, the density of the lungs was observed to decrease over the period during which the antibody was administered and to remain stable after therapy had ceased. When considered together, these data indicate that inhibition of CTGF can prevent and reverse the process of fibrosis
Urinary kallikrein excretion is related to renal function change and inflammatory status in chronic kidney disease patients receiving angiotensin II receptor blocker treatment
Mechanisms by which bradykinin promotes fibrosis in vascular smooth muscle cells: role of TGF-β and MAPK
Effects of amino acid infusion on renal hemodynamics. Role of endothelium-derived relaxing factor.
Ingestion of protein or intravenous infusion of amino acids acutely elevates glomerular filtration rate (GFR) and renal plasma flow (RPF) by unknown mechanisms. Endotheliumderived relaxing factor (EDRF), now known to be nitric oxide derived from metabolism L-arginine, participates in local regulation of vascular tone. To investigate the hypothesis that EDRF may participate in the renal vasodilatation and increased GFR after amino acid infusion, we characterized the effect of inhibition of EDRF synthesis with N-monomethyl L-arginine (LNMMA) on basal renal hemodynamics and the response to infusion of a 10% mixed amino acid solution (1 ml/hr i.v.) in the rat. Renal arterial infusion of LNMMA (500/μ/kg/min) resulted in a significant increase in mean arterial pressure, decreases in GFR (20%) and RPF (44%), and a significant increase in filtration fraction. Pretreatment with the angjotensin II receptor antagonist Sar-Gly-angiotensin II did not prevent the increase in blood pressure but blunted the decreases in GFR (11%) and RPF (27%) after LNMMA infusion. Amino acid infusion in the untreated, fasted rat resulted in no change in blood pressure but significant increases in GFR and RPF; these effects were completely inhibited by intrarenal LNMMA but not an equihypertensive intravenous infusion of phenylephrine. In summary, EDRF participates in regulation of basal renal hemodynamics. Furthermore, amino acidinduced hyperfiltration and renal vasodilatation are completely prevented by inhibition EDRF synthesis. We conclude that EDRF may participate in the renal hemodynamic response to amino acid infusion
Effects of Insulin and Insulin-like Growth Factor-I on Renin Gene Expression in the Renal Cortical Cells of Ovine Fetuses
Creatinine metabolite, HMH (5-hydroxy-1-methylhydantoin; NZ-419), modulates bradykinin-induced changes in vascular smooth muscle cells
The Influence of L - Tryptophan Peroral Load on Glomerular Filtration Rate in Chronic Glomerulonephritis and Chronic Renal Failure
Glomerular hyperfiltration in type 1 diabetes mellitus results from primary changes in proximal tubular sodium handling without changes in volume expansion.
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47800.pdf (publisher's version ) (Closed access)BACKGROUND: Glomerular hyperfiltration plays a role in the pathophysiology of diabetic nephropathy. An increase in the glomerular filtration rate (GFR) could result from primary actions at the glomerular/vascular level or could be the consequence of a primary increase in proximal tubular sodium reabsorption resulting in systemic volume expansion. Recently it was hypothesized that an increase in sodium reabsorption may lead to glomerular hyperfiltration through the tubulo-glomerular feedback mechanism (tubular-hypothesis) without volume expansion. DESIGN: We have studied 54 normoalbuminuric patients with type 1 diabetes. The GFR was measured by inulin clearance. Proximal and distal sodium reabsorption were calculated according to standard formulas using the free water clearance technique. Plasma volume, measured by the (125)I-albumin method, atrial natriuretic peptide (ANP) and the second messenger cyclic guanosine-3,5-monophosphate (c-GMP) were used as markers of extracellular volume expansion. RESULTS: Glomerular hyperfiltration (GFR >or= 130 mL min(-1) 1.73 m(-2)) was present in 14 out of 55 patients with diabetes (25%). There were no differences in plasma volume between normo-(NF) and hyper-filtrating (HF) patients (2933 +/- 423 in NF vs. 3026 +/- 562 mL in HF, NS). Also plasma ANP and c-GMP levels were not significantly different between the groups. The fractional proximal reabsorption of sodium was significantly increased in HF [fPRNa(+) (%) 90.1 +/- 2.0 vs. 91.5 +/- 1.6, P = 0.02]. There were no differences in distal sodium reabsorption or distal sodium load (approximately macula densa concentration of NaCl) in both groups. CONCLUSIONS: Our data suggest that the primary event in diabetic glomerular hyperfiltration is an increase in proximal tubular sodium reabsorption. They do not support the hypothesis that systemic volume expansion or ANP mediate glomerular hyperfiltration in patients with normoalbuminuric type 1 diabetes. As such, changes in tubular sodium handling most probably influence tubulo-glomerular feedback