Serum amyloid A and Janus kinase 2 in a mouse model of diabetic kidney disease.

Background: Serum amyloid A (SAA), a potent inflammatory mediator, and Janus kinase 2 (JAK2), an intracellular signaling kinase, are increased by diabetes. The aims were to elucidate: 1) a JAK2-mediated pathway for increased SAA in the kidneys of diabetic mice; 2) a JAK2-SAA pathway for inflammation in podocytes.

Methods: Akita diabetic mice (129S6) with podocyte JAK2 overexpression and angiotensin II infusion (4 weeks) were given a JAK1,2 inhibitor (LY03103801, 3 mg/kg/day orally for the last two weeks).

Association of Serum Amyloid A with Kidney Outcomes and All-Cause Mortality in American Indians with Type 2 Diabetes.

Background: Serum amyloid A (SAA) induces inflammation and apoptosis in kidney cells and is found to be causing the pathologic changes that are associated with diabetic kidney disease (DKD). Higher serum SAA concentrations were previously associated with increased risk of end-stage renal disease (ESRD) and death in persons with type 2 diabetes and advanced DKD. We explored the prognostic value of SAA in American Indians with type 2 diabetes without DKD or with early DKD.

Serum amyloid a and risk of death and end-stage renal disease in diabetic kidney disease.

Aims: To determine if serum levels of serum amyloid A (SAA) predict death and end-stage renal disease in a cohort of people with diabetic kidney disease.

Methods: In a longitudinal cohort study of 135 participants with type 2 diabetes and diabetic kidney disease, serum samples were assayed for SAA. Censored time-to-event analyses in Cox-proportional hazard models were utilized to assess SAA as a predictor of the primary outcome of death and end-stage renal disease.

Novel Therapies for Diabetic Kidney Disease: Storied Past and Forward Paths.

IN BRIEF Current therapeutic approaches are only moderately efficacious at preventing the progression of diabetic kidney disease (DKD). As the number of people with DKD continues to rise worldwide, there is an urgent need for novel therapies. A better understanding of the root causes and molecular mechanisms of DKD pathogenesis has enabled the identification of numerous new therapeutic targets, including advanced glycation end products, reactive oxygen species, protein kinase C, and serum amyloid A.

Serum amyloid A and inflammation in diabetic kidney disease and podocytes.

Inflammatory pathways are central mechanisms in diabetic kidney disease (DKD). Serum amyloid A (SAA) is increased by chronic inflammation, but SAA has not been previously evaluated as a potential DKD mediator. The aims of this study were to determine whether SAA is increased in human DKD and corresponding mouse models and to assess effects of SAA on podocyte inflammatory responses.

Glomerular cell death and inflammation with high-protein diet and diabetes.

Background: Overfeeding amino acids (AAs) increases cellular exposure to advanced glycation end-products (AGEs), a mechanism for protein intake to worsen diabetic kidney disease (DKD). This study assessed receptor for AGE (RAGE)-mediated apoptosis and inflammation in glomerular cells exposed to metabolic stressors characteristic of high-protein diets and/or diabetes in vitro with proof-of-concept appraisal in vivo.

Methods: Mouse podocytes and mesangial cells were cultured under control and metabolic stressor conditions: (i) no addition; (ii) increased AAs (4-6-fold>control); (iii) high glucose (HG, 30.

Oxidative stress mediates protein kinase C activation and advanced glycation end product formation in a mesangial cell model of diabetes and high protein diet.

Background/aims: High levels of glucose and/or amino acids increase advanced glycation end products (AGE) and activate protein kinase C (PKC), a key signal for injury in mesangial cells. The aim was to determine whether oxidative stress mediates bidirectional interactions between AGE and PKC ('cross-activation') in this model.

Methods: Rat mesangial cells were examined after 48 h of exposure to: high glucose (30.

Amino acids injure mesangial cells by advanced glycation end products, oxidative stress, and protein kinase C.

Background: In diabetes, high intake of dietary protein exacerbates responses associated with kidney damage. Increased levels of amino acids could injure cells by providing free amino groups for glycation reactions leading to advanced glycation end products (AGEs).

Methods: Rat mesangial cells were cultured with increased amino acids designed to resemble protein feeding, high glucose (30.

Amino acids induce indicators of response to injury in glomerular mesangial cells.

High-protein diets exacerbate glomerular hyperfiltration and the progression of diabetic nephropathy. The purpose of this study was to determine whether amino acids also produce nonhemodynamic injury in the glomerulus. When rat mesangial cells were cultured with an amino acid mixture designed to replicate the composition in plasma after protein feeding, production of mRNA (Northern blot analysis) and/or protein (ELISA or Western blot analysis) for transforming growth factor-beta1 (TGF-beta1), fibronectin, thrombospondin-1 (TSP-1), and collagen IV were enhanced in a manner comparable to a culture with high glucose (30.

Effects of amino acids and glucose on mesangial cell aminopeptidase a and angiotensin receptors.

Background: High protein diets and diabetes increase renal renin angiotensin system (RAS) activity, which is associated with glomerular injury. Aminopeptidase A (APA) is a cell surface metalloprotease that degrades angiotensin II (AII) in the mesangium. Mesangial cells (MC) also possess receptors for AII; the type 1 (AT1 receptor) promotes proliferation and fibrosis, while the type 2 (AT2 receptor) opposes these effects.