Deletion of protein tyrosine phosphatase SHP-1 restores SUMOylation of podocin and reverses the progression of diabetic kidney disease.

Both clinical and experimental data suggest that podocyte injury is involved in the onset and progression of diabetic kidney disease (DKD). Although the mechanisms underlying the development of podocyte loss are not completely understood, critical structural proteins such as podocin play a major role in podocyte survival and function. We have reported that the protein tyrosine phosphatase SHP-1 expression increased in podocytes of diabetic mice and glomeruli of patients with diabetes.

Reduction of DUSP4 contributes to podocytes oxidative stress, insulin resistance and diabetic nephropathy.

Podocytes are insulin-sensitive cells, and their loss is critical in diabetic nephropathy (DN) progression that could lead to end-stage kidney disease. We have previously shown that decreased DUSP4 expression caused elevated JNK phosphorylation in the diabetic kidney and worsened DN characteristics. Yet, the role of DUSP4 in diabetic podocyte insulin resistance and the progression of DN remains unclear.

Saturated fatty acids induce insulin resistance in podocytes through inhibition of IRS1 via activation of both IKKβ and mTORC1.

Diabetic nephropathy (DN), a microvascular complication of diabetes, is the leading cause of end-stage renal disease worldwide. Multiple studies have shown that podocyte dysfunction is a central event in the progression of the disease. Beside chronic hyperglycemia, dyslipidemia can induce insulin resistance and dysfunction in podocytes.

Interlaboratory bias of albuminuria and proteinuria in hypertensive pregnancy.

Background: Measurement of proteinuria in women with hypertensive disorders of pregnancy is of major importance in the diagnosis and management of preeclampsia. Urinary protein/creatinine ratio, which is commonly used to detect kidney damage in preeclampsia, suffers from important analytical limitations, including poor harmonization of results between laboratories. Adoption of albuminuria could help reduce interlaboratory bias, since methods used to quantify it are better harmonized.

Diabetes-Induced DUSP4 Reduction Promotes Podocyte Dysfunction and Progression of Diabetic Nephropathy.

Diabetic nephropathy (DN) remains the leading cause of end-stage renal disease. Hyperglycemia-induced podocyte dysfunction is a major contributor of renal function impairment in DN. Previous studies showed that activation of mitogen-activated protein kinase (MAPK) in diabetes promotes podocyte dysfunction and cell death.

Regulation of Nephrin Phosphorylation in Diabetes and Chronic Kidney Injury.

Diabetes is the leading cause of microalbuminuria and end-stage renal failure in industrial countries. Disruption of the filtration barrier, seen in almost all nephrotic diseases and diabetes, is the result of the loss or effacement of the podocyte foot process, notably damage of proteins within the slit diaphragm such as nephrin. For many years, nephrin has been viewed as a structural component of the slit diaphragm.

Persistent Insulin Resistance in Podocytes Caused by Epigenetic Changes of SHP-1 in Diabetes.

Poor glycemic control profoundly affects protein expression and the cell signaling action that contributes to glycemic memory and irreversible progression of diabetic nephropathy (DN). We demonstrate that SHP-1 is elevated in podocytes of diabetic mice, causing insulin unresponsiveness and DN. Thus, sustained SHP-1 expression caused by hyperglycemia despite systemic glucose normalization could contribute to the glycemic memory effect in DN.

Increased SHP-1 protein expression by high glucose levels reduces nephrin phosphorylation in podocytes.

Nephrin, a critical podocyte membrane component that is reduced in diabetic nephropathy, has been shown to activate phosphotyrosine signaling pathways in human podocytes. Nephrin signaling is important to reduce cell death induced by apoptotic stimuli. We have shown previously that high glucose level exposure and diabetes increased the expression of SHP-1, causing podocyte apoptosis.

PKCδ impaired vessel formation and angiogenic factor expression in diabetic ischemic limbs.

Decreased collateral vessel formation in diabetic peripheral limbs is characterized by abnormalities of the angiogenic response to ischemia. Hyperglycemia is known to activate protein kinase C (PKC), affecting the expression and activity of growth factors such as vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF). The current study investigates the role of PKCδ in diabetes-induced poor collateral vessel formation and inhibition of angiogenic factors expression and actions.

Expression of SHP-1 induced by hyperglycemia prevents insulin actions in podocytes.

Renal podocyte apoptosis is an early event of diabetic nephropathy progression. Insulin action is critical for podocyte survival. Previous studies demonstrated that Src homology-2 domain-containing phosphatase-1 (SHP-1) is elevated in renal cortex of type 1 diabetic mice; we hypothesized that hyperglycemia-induced SHP-1 expression may affect insulin actions in podocytes.