Soluble CD40 ligand directly alters glomerular permeability and may act as a circulating permeability factor in FSGS.

CD40/CD40 ligand (CD40L) dyad, a co-stimulatory bi-molecular complex involved in the adaptive immune response, has also potent pro-inflammatory actions in haematopoietic and non-haematopoietic cells. We describe here a novel role for soluble CD40L (sCD40L) as modifier of glomerular permselectivity directly acting on glomerular epithelial cells (GECs). We found that stimulation of CD40, constitutively expressed on GEC cell membrane, by the sCD40L rapidly induced redistribution and loss of nephrin in GECs, and increased albumin permeability in isolated rat glomeruli.

Blockade of Thrombopoietin Reduces Organ Damage in Experimental Endotoxemia and Polymicrobial Sepsis.

Background And Purpose: Thrombopoietin (TPO), a growth factor primarily involved in thrombopoiesis may also have a role in the pathophysiology of sepsis. In patients with sepsis, indeed, TPO levels are markedly increased, with disease severity being the major independent determinant of TPO concentrations. Moreover, TPO increases and correlates with ex vivo indices of platelet activation in patients with burn injury upon sepsis development, and may contribute to depress cardiac contractility in septic shock.

Telomere shortening in Ph-negative chronic myeloproliferative neoplasms: a biological marker of polycythemia vera and myelofibrosis, regardless of hydroxycarbamide therapy.

The purpose of this study was to investigate telomere length (TL) in Ph-negative chronic myeloproliferative neoplasms (Ph-neg-CMNs), and the possible association of TL with disease progression and hydroxycarbamide (HU) treatment. TL was analyzed in peripheral blood samples from 239 patients with Ph-neg-CMNs, including polycythemia vera (PV), essential thrombocythemia and myelofibrosis (MF), and compared with age-matched healthy control subjects (CTR), along with some cases of secondary erythrocytosis (SE). More than half of the patients with CMN received at least 1 year of cytoreduction, mainly HU, before TL analysis.

The aging effect of chemotherapy on cultured human mesenchymal stem cells.

Various agents, including chemotherapeutic drugs, can induce cell senescence. However, the mechanisms involved in the aging pathway, particularly the stress that chemotherapy imposes on telomeres, are still undefined. To address these issues, human mesenchymal stem cells (MSCs) were assessed as target cells to investigate the initiation of the aging process by chemotherapy.

A novel role of thrombopoietin as a physiological modulator of coronary flow.

Thrombopoietin (TPO) is known for its ability to stimulate platelet production. However, little is currently known whether TPO plays a physiological function in the heart. The potential vasodilatory role of TPO was tested on the isolated rat heart.

Thrombopoietin modulates cardiac contractility in vitro and contributes to myocardial depressing activity of septic shock serum.

Thrombopoietin (TPO) is a humoral growth factor that has been shown to increase platelet activation in response to several agonists. Patients with sepsis have increased circulating TPO levels, which may enhance platelet activation, potentially participating to the pathogenesis of multi-organ failure. Aim of this study was to investigate whether TPO affects myocardial contractility and participates to depress cardiac function during sepsis.

Thrombopoietin contributes to enhanced platelet activation in cigarette smokers.

Objectives: Thrombopoietin (TPO) is a humoral growth factor that primes platelet activation in response to several agonists. We recently showed that TPO enhances platelet activation in unstable angina and sepsis. Aim of this study was to investigate the role of TPO in platelet function abnormalities described in cigarette smokers.

HIV-1 Tat reduces nephrin in human podocytes: a potential mechanism for enhanced glomerular permeability in HIV-associated nephropathy.

Objective: To determine whether HIV-1 Tat may directly alter glomerular permeability in HIV-associated nephropathy (HIVAN).

Design: Heavy proteinuria is a hallmark of HIVAN. The slit diaphragm is the ultimate glomerular filtration barrier critical for maintaining the efficiency of the ultrafiltration unit of the kidney.

Direct effect of plasma permeability factors from patients with idiopatic FSGS on nephrin and podocin expression in human podocytes.

The presence of circulating plasma factors (PF) altering renal permeability to proteins has been previously described in patients with focal segmental glomerulosclerosis (FSGS). Since these patients show reduced nephrin and podocin expression at renal biopsy, we evaluated the effect of serum and PF from patients with FSGS on nephrin and podocin expression in human podocytes. We studied 7 sera from patients with steroid-resistant FSGS, 3 from patients with nephrotic syndrome caused by non-immune disease, and 6 from healthy subjects.

Statins prevent oxidized LDL-induced injury of glomerular podocytes by activating the phosphatidylinositol 3-kinase/AKT-signaling pathway.

The injury of podocytes is associated with alterations of the glomerular size-selective barrier to proteins. In this study, oxidized LDL (oxLDL) but not native LDL induced apoptosis in human cultured podocytes and reduced Akt activity and P-Akt/Akt ratio. Moreover, oxLDL-induced redistribution and loss of nephrin, an adhesion molecule specific for the glomerular slit diaphragm.