Cleavage of periostin by MMP9 protects mice from kidney cystic disease.

The matrix metalloproteinase MMP9 influences cellular morphology and function, and plays important roles in organogenesis and disease. It exerts both protective and deleterious effects in renal pathology, depending upon its specific substrates. To explore new functions for MMP9 in kidney cysts formation and disease progression, we generated a mouse model by breeding juvenile cystic kidney (jck) mice with MMP9 deficient mice.

Collecting duct cells show differential retinoic acid responses to acute versus chronic kidney injury stimuli.

Retinoic acid (RA) activates RA receptors (RAR), resulting in RA response element (RARE)-dependent gene expression in renal collecting duct (CD). Emerging evidence supports a protective role for this activity in acute kidney injury (AKI) and chronic kidney disease (CKD). Herein, we examined this activity in RARE-LacZ transgenic mice and by RARE-Luciferase reporter assays in CD cells, and investigated how this activity responds to neurotransmitters and mediators of kidney injury.

Acidic organelles mediate TGF-β1-induced cellular fibrosis via (pro)renin receptor and vacuolar ATPase trafficking in human peritoneal mesothelial cells.

TGF-β1, which can cause renal tubular injury through a vacuolar-type H-ATPase (V-ATPase)-mediated pathway, is induced by the glucose degradation product methylglyoxal to yield peritoneal injury and fibrosis. The present study investigated the roles of V-ATPase and its accessory protein, the (pro)renin receptor, in peritoneal fibrosis during peritoneal dialysis. Rats daily administered 20 mM methylglyoxal intraperitoneally developed significant peritoneal fibrosis after 7 days with increased expression of TGF-β and V-ATPase, which was reduced by the inhibition of V-ATPase with co-administration of 100 mM bafilomycin A1.

Anoctamin 6 is localized in the primary cilium of renal tubular cells and is involved in apoptosis-dependent cyst lumen formation.

Primary cilia are antenna-like structures projected from the apical surface of various mammalian cells including renal tubular cells. Functional or structural defects of the cilium lead to systemic disorders comprising polycystic kidneys as a key feature. Here we show that anoctamin 6 (ANO6), a member of the anoctamin chloride channel family, is localized in the primary cilium of renal epithelial cells in vitro and in vivo.

The SAM domain of ANKS6 has different interacting partners and mutations can induce different cystic phenotypes.

The ankyrin repeat and sterile α motif (SAM) domain-containing six gene (Anks6) is a candidate for polycystic kidney disease (PKD). Originally identified in the PKD/Mhm(cy/+) rat model of PKD, the disease is caused by a mutation (R823W) in the SAM domain of the encoded protein. Recent studies support the etiological role of the ANKS6 SAM domain in human cystic diseases, but its function in kidney remains unknown.

Complete remission of monoclonal gammopathy with ocular and periorbital crystal storing histiocytosis and Fanconi syndrome.

A 62-year-old woman presented with crystalline keratopathy, crystal-storing histiocytosis, Fanconi syndrome, and a serum monoclonal IgG-κ and urinary κ light chain. Histology and electron microscopy studies revealed the presence of crystals within macrophages in multiple eye sites, in the kidney and in the bone marrow. The variable domain of the pathogenic κ light chain related to the Vk1-39 gene that was also involved in most previously reported cases of Fanconi syndrome.

LG3 fragment of endorepellin is a possible biomarker of severity in IgA nephropathy.

IgA nephropathy (IgAN), the most common primary glomerulonephritis, is characterized by deposition of IgA in the glomerular mesangium. The diagnosis of IgAN still requires a kidney biopsy that cannot easily be repeated in the same patient during follow-up. Therefore, identification of noninvasive urinary biomarkers would be very useful for monitoring patients with IgAN.

Acute renal failure with lambda light chain-derived crystals in a patient with IgD myeloma.

Kidney involvement with immunoglobulin crystals usually relates to a light chain of the kappa type, in MGUS or smoldering myeloma, frequently causing Fanconi's syndrome with progressive renal insufficiency. We report on a case with severe myeloma featuring lambda light chain-derived crystals and acute kidney injury. Histology showed acute tubular necrosis and tubule obstruction with crystals, which were also abundant inside tubule epithelial cells, macrophages and bone marrow plasma cells.

Matrix metalloproteinases in kidney disease progression and repair: a case of flipping the coin.

Matrix metalloproteinases (MMPs) have pleiotropic enzymatic actions that go far beyond degradation of extracellular matrix. Both the multiplicity of their targets and the complexity of their regulation account for a variety of biological effects. In renal diseases, MMP effects may be different and/or opposite during the different phases of the pathology evolution.

Urokinase (u-PA) is produced by collecting duct principal cells and is post-transcriptionally regulated by SV40 large-T, arginine vasopressin, and epidermal growth factor.

We have analyzed the expression and regulation of plasminogen activators (PA) in principal cells of the renal collecting duct. We used a rabbit principal cell line (RC.SVtsA58) infected with the temperature-sensitive SV40 strain tsA58.

N-linked glycosylation of macrophage-derived PAF-AH is a major determinant of enzyme association with plasma HDL.

Human plasma PAF-AH (platelet-activating factor-acetylhydrolase) is a Ca(2)+-independent phospholipase A2 of hematopoietic origin associated with LDL and HDL; it degrades PAF and oxidizes phospholipids. We show that human macrophages synthesize PAF-AH as a premedial Golgi precursor containing high mannose N-linked glycans. Secreted PAF-AH possesses a molecular mass of approximately 55 kDa and contains mature N-linked glycans.

Do matrix metalloproteinases MMP-2 and MMP-9 (gelatinases) play a role in renal development, physiology and glomerular diseases?

Metalloproteinases MMP-2 and MMP-9 (also called gelatinases) are involved in cell invasion and in embryonic development and organogenesis. A growing number of reports suggest that MMP-2 and MMP-9 play some role in renal development, renal tubule physiology and glomerular pathophysiology. This editorial will focus on recent controversial data, especially those obtained from studies on MMP-9-deficient mice, which shed new light on the functions of gelatinases in normal and diseased kidneys.

Matrix metalloproteinase 2 (MMP2) and MMP9 are produced by kidney collecting duct principal cells but are differentially regulated by SV40 large-T, arginine vasopressin, and epidermal growth factor.

We analyzed the expression and regulation of matrix metalloproteinase 2 (MMP2) and MMP9 gelatinases in a rabbit kidney collecting duct principal cell line (RC.SVtsA58) (Prié, D., Ronco, P.

Hyperosmolality suppresses but TGF beta 1 increases MMP9 in human peritoneal mesothelial cells.

Peritoneal mesothelial cells are directly exposed to hyperosmolar dialysates which may enhance extracellular matrix accumulation and hence compromise ultrafiltration. Because these cells are laid on a type IV collagen containing basement membrane, we examined the pattern of type IV collagenases produced by cultured human mesothelial cells and their regulation by hyperosmolality and TGF beta 1. A cell line (HMrSV5) exhibiting major features of normal peritoneal mesothelial cells was derived from a primary culture retrovirally transduced with SV40 large-T antigen.

SV40 large-T oncogene inhibits transcription of perlecan-related proteoglycans but stimulates hyaluronan synthesis in a temperature-sensitive renal-tubule principal cell line.

We have analyzed the effects of SV40 large-T oncogene on proteoglycan (PG) synthesis in a temperature-sensitive SV40-transformed renal cell line. Cells shifted from permissive (33 degrees C) to restrictive (39.5 degrees C) temperature, acquired within 48 h the phenotype of principal cells of the renal collecting tubule.

Dramatic changes of sulfated proteoglycans composition in a tumorigenic SV-40-transformed renal proximal-tubule cell line.

To characterize the sulfated proteoglycans (PGs) alterations associated with malignant transformation of epithelial cells in vitro, the localization, charge, size, and composition of cell-associated and secreted sulfated PGs have been compared in rabbit renal proximal-tubule cells in primary culture (Ronco et al., 1990) and in a derived SV-40 transformed cell line (RC.SV1) exhibiting a proximal phenotype and high tumor-inducing ability (Vandewalle et al.

Characterization of a simian virus 40-transformed human podocyte cell line producing type IV collagen and exhibiting polarized response to atrial natriuretic peptide.

Biology of glomerular visceral epithelial cells ("podocytes") and their role in inflammatory process remain obscure, partly because of the lack of well-differentiated podocyte cultures. We have established a human cell line by transfecting with a replication-defective SV40 plasmid (pSVHB1), a primary culture of podocytes derived from an enriched preparation of unencapsulated glomeruli free of tubule and Bowman's capsule contaminants. Podocyte specificity of the primary culture was assessed by a dual immunomorphological and functional approach.

Activation of the simian virus 40 (SV40) genome abrogates sensitivity to AVP in a rabbit collecting tubule cell line by repressing membrane expression of AVP receptors.

To analyze the role of SV40 genome in the phenotypic alterations previously observed in SV40-transformed cell lines, we infected rabbit renal cortical cells with a temperature-sensitive SV40 mutant strain (tsA58) and compared the cell phenotypes at temperatures permissive (33 degrees C) and restrictive (39.5 degrees C) for SV40 genome expression. At both temperatures, the resulting cell line (RC.