RESUMO
TAM receptors (Tyro3, Axl, and Mer) have been implicated in innate immunity. Circulating TAM receptor soluble forms (sTyro3, sAxl, sMer) are related to autoimmune disorders. We investigated TAM and their ligand protein S in patients with diabetes. Urinary and plasma levels of protein S, sTyro3, sAxl, and sMer were determined in 126 patients with diabetes assigned to a normoalbuminuric or macroalbuminuric (urinary albumin excretion <30 mg/24 hours and >300 mg/24 hours, respectively) study group and 18 healthy volunteers. TAM and protein S immunostaining was performed on kidney biopsy specimens from patients with diabetic nephropathy (n = 9) and controls (n = 6). TAM expression and shedding by tubular epithelial cells were investigated by PCR and enzyme-linked immunosorbent assay in an in vitro diabetes model. Patients with macroalbuminuria diabetes had higher circulating levels of sMer and more urinary sTyro3 and sMer than normoalbuminuric diabetics. Increased clearance of sTyro3 and sMer was associated with loss of tubular Tyro3 and Mer expression in diabetic nephropathy tissue and glomerular depositions of protein S. During in vitro diabetes, human kidney cells had down-regulation of Tyro3 and Mer mRNA and increased shedding of sTyro3 and sMer. Renal injury in diabetes is associated with elevated systemic and urine levels of sMer and sTyro3. This is the first study reporting excretion of sTAM receptors in urine, identifying the kidney as a source of sTAM.
Assuntos
Nefropatias Diabéticas/metabolismo , Proteína S/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Receptores Proteína Tirosina Quinases/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Linhagem Celular , Nefropatias Diabéticas/sangue , Nefropatias Diabéticas/urina , Feminino , Humanos , Glomérulos Renais/metabolismo , Masculino , Pessoa de Meia-Idade , Proteína S/urina , Proteínas Proto-Oncogênicas/sangue , Proteínas Proto-Oncogênicas/urina , Receptores Proteína Tirosina Quinases/sangue , Receptores Proteína Tirosina Quinases/urina , c-Mer Tirosina Quinase , Receptor Tirosina Quinase AxlRESUMO
Plasma and urine concentrations of protein S were measured in five children with steroid-resistant nephrotic syndrome. It was found that plasma free protein S was reduced in three out of the five patients studied. Thus, acquired free protein S deficiency does occur in children with nephrotic syndrome and is one of many factors which may place them at risk for a thromboembolic event.
Assuntos
Síndrome Nefrótica/complicações , Deficiência de Proteína S/etiologia , Proteína S/análise , Esteroides/farmacologia , Criança , Pré-Escolar , Creatinina/urina , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Transplante de Rim , Masculino , Síndrome Nefrótica/metabolismo , Proteína S/urina , Deficiência de Proteína S/metabolismo , Proteinúria/etiologia , Fatores de Risco , Tromboembolia/etiologiaRESUMO
Nephrotic syndrome (NS) is associated with an increased incidence of various thromboembolic complications in adult patients. It was found to be due to elevated factor IX (FIX) F.VII, F.VIII, F.V, fibrinogen, thrombocytosis and increased platelet reactivity. Acquired AT-III deficiency, reduced functional levels of protein S and reduced activity of protein C were also reported. We evaluated 15 children aged 1 to 13 years. Thirteen of these children suffered from nephrotic syndrome and two others had non-nephrotic proteinuria. All patients but one were normotensive. Two patients were not steroid responsive. Serum creatinine was normal for age in 14 patients. Kidney biopsy was carried out only in three children. Haemostatic parameters included protein C and S antigenicity in plasma and urine. Plasma levels of protein C and protein S were within the normal range. Protein C antigenicity in urine was increased in five children out of 14 examined. Protein S in urine was increased in seven out of 12 children examined. No thromboembolic phenomena were documented even though protein C and protein S antigenicity were identified in the urine.