Serum syndecan-1, hyaluronan and thrombomodulin levels in patients with lupus nephritis.

Objectives: We investigated circulating syndecan-1, HA and thrombomodulin levels in patients with biopsy-proven Class III/IV ± V LN and their clinico-pathological associations. Patients with non-renal SLE or non-lupus chronic kidney disease, and healthy subjects served as controls.

Methods: Serum syndecan-1, HA and thrombomodulin levels were determined by ELISAs.

Effect of mycophenolate and rapamycin on renal fibrosis in lupus nephritis.

Lupus nephritis (LN) leads to chronic kidney disease (CKD) through progressive fibrosis. Mycophenolate inhibits inosine monophosphate dehydrogenase and is a standard treatment for LN. The mammalian or mechanistic target of rapamycin (mTOR) pathway is activated in LN.

miR-200c Prevents TGF-β1-Induced Epithelial-to-Mesenchymal Transition and Fibrogenesis in Mesothelial Cells by Targeting ZEB2 and Notch1.

Peritoneal fibrosis and loss of transport function is a common complication contributing to adverse outcomes in patients on long-term peritoneal dialysis (PD). Epithelial-to-mesenchymal transition (EMT) in mesothelial cells is a salient feature, but its triggering mechanisms remain obscure. Dysregulation of microRNA (miR) expression is implicated in EMT and tissue fibrosis.

Annexin II-binding immunoglobulins in patients with lupus nephritis and their correlation with disease manifestations.

Annexin II on mesangial cell surface mediates the binding of anti-dsDNA antibodies and consequent downstream inflammatory and fibrotic processes. We investigated the clinical relevance of circulating annexin II-binding immunoglobulins (Igs) in patients with severe proliferative lupus nephritis, and renal annexin II expression in relation to progression of nephritis in New Zealand Black and White F1 mice (NZBWF1/J) mice. Annexin II-binding Igs in serum were measured by ELISA.

Binding of anti-dsDNA antibodies to proximal tubular epithelial cells contributes to renal tubulointerstitial inflammation.

Immune deposits are often observed along the tubular basement membrane in patients with lupus nephritis, but the role of anti-dsDNA antibody (Ab) deposition on tubulointerstitial inflammation remains to be investigated. We examined the effect of human polyclonal anti-dsDNA Abs on inflammatory processes in cultured proximal renal tubular epithelial cells (PTEC, HK-2 cells) and their association with serum levels of interleukin (IL)-6, IL-8 and monocyte chemoattractant protein-1 (MCP-1) in patients. Binding of anti-dsDNA Abs to HK-2 cells was investigated by cellular ELISA, flow cytometry and immunohistochemistry.

Distinct effects of mycophenolate mofetil and cyclophosphamide on renal fibrosis in NZBWF1/J mice.

Progression to chronic renal failure varies between patients with lupus nephritis. We compared the effects of mycophenolate mofetil (MMF) and cyclophosphamide (CTX), on renal histology and cellular pathways of fibrosis in murine lupus nephritis. Female NZBWF1/J mice were randomized to treatment with vehicle, methylprednisolone (MP) alone, MMF + MP or CTX + MP for up to 12 weeks, and the effects on clinical parameters, renal histology, and fibrotic processes were investigated.

Anti-dsDNA antibody induces soluble fibronectin secretion by proximal renal tubular epithelial cells and downstream increase of TGF-β1 and collagen synthesis.

The level of anti-dsDNA antibodies correlates with disease activity in lupus nephritis, but their role in pathogenic mechanisms remains to be defined. We investigated the effect of anti-dsDNA antibodies isolated from lupus nephritis patients on fibronectin synthesis and downstream fibrogenesis in proximal renal tubular epithelial cells (PTEC). Kidney biopsies were obtained from patients with active severe proliferative lupus nephritis.

Cellular cholesterol transport proteins in diabetic nephropathy.

Background: Lipid accumulation has been shown to accelerate renal injury, and the intracellular accumulation of lipids may be caused by alterations in synthesis as well as lipid uptake and efflux. We have investigated the role of cellular cholesterol transport proteins including adenosine triphosphate binding cassette transporter A1 (ABCA1), G1 (ABCG1) and scavenger receptor class B type I (SR-BI) in diabetic nephropathy.

Methods: Protein expression and the ability to mediate cholesterol efflux of ABCA1, ABCG1 and SR-BI was determined in human renal mesangial cells and proximal tubular epithelial cells cultured under normal or high glucose conditions.

Sulodexide decreases albuminuria and regulates matrix protein accumulation in C57BL/6 mice with streptozotocin-induced type I diabetic nephropathy.

Objective: Sulodexide is a mixture of glycosaminoglycans that may reduce proteinuria in diabetic nephropathy (DN), but its mechanism of action and effect on renal histology is not known. We investigated the effect of sulodexide on disease manifestations in a murine model of type I DN.

Methods: Male C57BL/6 mice were rendered diabetic with streptozotocin.