Circulating fibronectin contributes to mesangial expansion in a murine model of type 1 diabetes

Abstract

Fibronectin is ubiquitously expressed in the extracellular matrix, and its accumulation in the glomerular mesangium in diabetic nephropathy is associated with deterioration of renal function in these patients. However, the exact role of fibronectin in the pathogenesis of diabetic nephropathy remains unknown. To clarify this, we administered fluorescent-labeled plasma fibronectin to wild-type mice and found it to accumulate in the mesangium. Using liver-specific conditional-knockout mice to decrease circulating fibronectin, we reduced circulating fibronectin by more than 90%. In streptozotocin-induced diabetes of these knockout mice, the pronounced fall in circulating fibronectin resulted in a decrease in mesangial expansion by 25% and a decline in albuminuria by 30% compared to diabetic control mice. Indeed, the amount of fibronectin in the kidney was reduced, as was the total amount of collagen. In vitro experiments confirmed that matrix accumulation of fibronectin was enhanced by increasing fibronectin only, glucose only, or the combination of both. Thus, circulating fibronectin contributes to mesangial expansion and exacerbation of albuminuria in a murine model of type 1 diabetes.

Gold nanoparticles attenuate albuminuria by inhibiting podocyte injury in a rat model of diabetic nephropathy

“…The immunohistochemistry analysis demonstrated that diabetes was associated with an increase in the intensity of immunostaining for collagen IV, fibronectin, and TGF-β 1 (Fig. 3a, b), which are the major ECM proteins that lead to the development of the mesangial matrix expansion in the status of DN [25]. Consistent with the immunohistochemical findings, the levels of mRNA encoding for fibronectin and TGF-β 1 were significantly greater in the D than in the ND group (Fig.…”

Hydrogen sulphide mitigates homocysteine-induced apoptosis and matrix remodelling in mesangial cells through Akt/FOXO1 signalling cascade

“…Hyperhomocysteinemia (HHcy), an increased plasma homocysteine (Hcy) level is prevalent among patients with chronic kidney diseases (CKD) [1]. The mesangial cell provides architectural support for glomerular capillary loops and are crucial players in the initiation and progression of many kidney diseases [2,3]. Increased glomerular mesangial cell apoptosis / proliferation and excessive accumulation of extracellular matrix (ECM) protein leads to glomerulosclerosis in CKD patients [4,5]; similar results are also reported in experimental CKD animals [6][7][8].…”

Clopidogrel Reduces Fibronectin Accumulation and Improves Diabetes-Induced Renal Fibrosis

“…The imbalance between the synthesis and breakdown of the ECM induces glomerulosclerosis and tubulointerstitial fibrosis. Liver-specific FN conditional knockout mice had no circulating FN and these mice were protected from STD-induced T1D, renal fibrosis and albuminuria, suggesting a critical role of circulating FN in these events 6. The improvement of renal fibrosis in a hyperglycemic state is the most concerned aspect of the current treatment.…”