Progression of Diabetic Nephropathy Enhances the Plasma Osteopontin Level in Type 2 Diabetic Patients

Abstract

Abstract. Osteopontin (OPN) is thought to play multiple roles in the progression of atherosclerotic plaque including diabetic vascular complications. However, it still remains unclear whether the level of OPN in vivo is indeed clinically associated with the progression of diabetic complications. This study evaluated whether the levels of OPN in plasma and urine are correlated with the progression of diabetic complications, such as retinopathy, neuropathy, and nephropathy in patients with type 2 diabetes. In 229 patients with type 2 diabetes, OPN level in plasma and urine was evaluated by both the severity of diabetic complications, such as retinopathy, neuropathy, and nephropathy, and the clinical characteristics and the substantial laboratory findings. Plasma OPN level increased significantly with aging and the progression of diabetic nephropathy, especially at the stage of renal failure (p<0.05). However, the level was not related to the progression of retinopathy or neuropathy, or to laboratory findings, such as HbA1c or serum lipids. In contrast, urinary OPN level was not associated with diabetic complications in any of the subjects. There was no correlation between the plasma and urinary values of OPN. The results established that the plasma OPN was elevated in proportion to the progression of diabetic nephropathy, indicating that the plasma concentration may be a potential diagnostic predictor of diabetic end-stage renal disease.

The endothelin receptor antagonist avosentan ameliorates nephropathy and atherosclerosis in diabetic apolipoprotein E knockout mice

“…Similarly, expression of the gene encoding osteopontin was decreased in diabetic mice treated with avosentan. Osteopontin has been identified as a marker of mesangial expansion in the diabetic mouse kidney [29], the severity of diabetic nephropathy in patients [30] and development of atherosclerosis [31]. The decrease in osteopontin expression with avosentan treatment is therefore consistent with decreases in the expression of genes encoding AT1a, TGF-β and NF-κB p65 subunit, which stimulate and are stimulated by osteopontin [32].…”

Activation of Liver X Receptor Inhibits Osteopontin and Ameliorates Diabetic Nephropathy

“…In humans, the plasma OPN level is significantly correlated with the extent of coronary atherosclerosis. 7,8 Moreover, the OPN levels are particularly elevated in patients with type 2 diabetes, 9,10 and we showed that peroxisome proliferator-activated receptor a ligands suppress OPN expression in macrophages in vitro and that bezafibrate reduces plasma OPN levels in patients with type 2 diabetes. 11 These clinical studies provide evidence that OPN may play a causal role in the development of cardiovascular disease in humans.…”

“…31,32 OPN is a proinflammatory cytokine implicated in the chemoattraction of monocytes and development of diabetic nephropathy, 16,17 and its levels are significantly elevated in patients with diabetic nephropathy. 9,33 OPN transcription is induced in response to high glucose, 34 raising the possibility that increased OPN secretion in diabetes may play a direct causal role in the development of diabetic nephropathy. For many years, it has been well known that OPN is upregulated in the interstitium, especially the proximal tubules, in the diabetic kidney.…”

Osteopontin Is a Strong Predictor of Incipient Diabetic Nephropathy, Cardiovascular Disease, and All-Cause Mortality in Patients With Type 1 Diabetes

“…However, OPN was originally found in bone and shown to regulate the formation and calcification of bone tissue (7). Notably, OPN has also been linked to vascular remodelling and calcification, especially in diabetic arteries (8), and has been shown to associate with diabetic retinopathy (9) and nephropathy (10) in patients with type 2 diabetes (T2D), as well as cardiovascular disease (CVD) events in nondiabetic subjects with a history of coronary artery disease (CAD) (11). However, its role for late complications in patients with type 1 diabetes (T1D) is not known.…”