OBJECTIVETo study the clinicopathologic features of collagen III glomerulopathy and its cause, pathogenesis and prognosis.

METHODSFive cases of collagen III glomerulopathy that collected from 2005 to 2014 were observed by renal biopsy. The morphologic characteristics were studied by light microscopy, immunofluorescence, immunohistochemical and electron microscopy.

RESULTSThe glomerular mesangium became expansion but no hypercellularity, basement membrane appeared thickened. The glomeruli showed collagen type III deposit by immunohistochemistry method, and collagen fibers increased by electron microscopy. The patients often show serious proteinuria, nephrotic syndrome and renal function damage.

CONCLUSIONSCollagen III glomerulopathy is an idiopathic glomerular disease, characterized by massive accumulation of collagen type III within the glomerular mesangial areas and basement membrane. Collagen III glomerulopathy is extremely rare. The etiology and pathogenesis may relate to the abnormality of collagen III gene. There is no specific treatment for it and its prognosis is poor.

Basement Membrane ; metabolism ; Biopsy ; Collagen Type III ; genetics ; metabolism ; Female ; Fluorescent Antibody Technique ; Glomerular Mesangium ; metabolism ; Humans ; Immunohistochemistry ; Kidney Diseases ; etiology ; pathology ; Kidney Glomerulus ; pathology ; Microscopy, Electron ; Prognosis ; Proteinuria ; diagnosis

IgA nephropathy (IgAN) is recognized as the most common immune complex related to the cause of glomerulonephritis worldwide. The disease is characterized by the predominant deposition of underglycosylated IgA1 in the mesangial area of glomeruli. Dysregulation of the immune system plays an important role in the pathogenesis of IgAN. Abnormalities restricted to T lymphocytes and/or B lymphocytes activation could be a critical causative factor in the over-production of underglycosylated IgA1.
Antigen-Antibody Complex ; B-Lymphocytes ; Glomerular Mesangium ; Glomerulonephritis, IGA ; pathology ; Humans ; Immunoglobulin A ; chemistry ; T-Lymphocytes

OBJECTIVETo investigate whether FTY720 inhibits rat mesangial proliferation and extracellular matrix expansion through suppression of transforming growth factor β1-connective tissue growth factor (TGFβ1-CTGF) pathway, and to explore experimental evidence for its effect on mesangial proliferative glomerulonephritis.

METHODSA rat model of anti-Thy-1 mesangial proliferative glomerulonephritis was established and FTY720 intervention was performed. Periphery blood lymphocyte count, urine protein excretion, glomerular mesangial proliferation, protein and gene expression of TGFβ1 and CTGF and extracellular matrix protein including fibronectin, laminin and collagen IV in isolated glomeruli were documented at 1, 3 and 7 days after injection of anti-Thy-1 antibody.

RESULTSThe model group developed proteinuria at 1, 3 and 7 days after injection of anti-Thy-1 antibody, which were significantly higher [(27.9 ± 7.3), (63.5 ± 18.8) and (52.4 ± 15.4)mg/d, respectively] than those in the control group [(8.4 ± 2.4), (8.4 ± 2.1) and (10.4 ± 3.2) mg/d; respectively, P < 0.01]. FTY720 intervention group showed significantly decreased proteinuria at 3 and 7 days after injection [(31.4 ± 7.0), (25.5 ± 7.7) mg/d, respectively] than model group (P < 0.01), although higher than the control group (P < 0.01). After intervention for 3 and 7 days, FTY720 significantly down-regulated both TGFβ1 and CTGF gene and protein expression in cultured glomeruli, and suppressed the production of glomerular extracellular matrix protein secretion, leading to attenuated mesangial cell proliferation and extracellular matrix expansion in rat anti-Thy-1 mesangial proliferative glomerulonephritis.

CONCLUSIONFTY720 significantly attenuates mesangial proliferation and extracellular matrix expansion through inhibition of TGFβ1-CTGF pathway in rat, and thus ameliorates the development of anti-Thy-1 mesangial proliferative glomerulonephritis.

Animals ; Cell Proliferation ; Connective Tissue Growth Factor ; genetics ; metabolism ; Down-Regulation ; Extracellular Matrix Proteins ; metabolism ; Fingolimod Hydrochloride ; Gene Expression ; Glomerular Mesangium ; metabolism ; pathology ; Glomerulonephritis, Membranoproliferative ; immunology ; metabolism ; pathology ; Immunosuppressive Agents ; pharmacology ; Isoantibodies ; immunology ; Kidney Glomerulus ; metabolism ; pathology ; Male ; Propylene Glycols ; pharmacology ; Proteinuria ; urine ; Rats ; Rats, Wistar ; Signal Transduction ; drug effects ; Sphingosine ; analogs & derivatives ; pharmacology ; Thy-1 Antigens ; immunology ; Transforming Growth Factor beta1 ; genetics ; metabolism

Animals ; Arginine Vasopressin ; physiology ; Connective Tissue Growth Factor ; physiology ; Glomerular Mesangium ; pathology ; Humans ; Integrin alpha1beta1 ; physiology ; Kidney Diseases ; etiology ; Proto-Oncogene Protein c-ets-1 ; physiology

OBJECTIVETo investigate the effects of Haikun Shenxi on the expression of platelet-derived growth factor-BB (PDGF-BB) and mRNA in renal tissue of rats with adriamycin nephropathy.

METHODRat model was established by unilateral nephrectomy and injecting adriamycin intraperitoneally. The adriamycin-induced nephrotic rats were randomly divided into 6 groups: normal group, sham operation group, model group, lotensin treatment group, Haikun Shenxi low and high dose treatment groups (0.77, 0.08 mg x kg(-1). Ten weeks later, the 24 hour urine protein and blood biochemistry examinations and renal pathologic changes were observed, and the expression of PDGF-BB and mRNA was measured using immunohistochemical method.

RESULTCompared with model group, proteinuria and the levels of serum creatinine (Scr) , urea nitrogen (BUN) were decreased obviously in both Haikun Shenxi low and high dose groups. The expression of PDGF-BB and mRNA was mostly presented in cytoplasm of renal tubular epithelial cells and mesangial area, and it could be reduced significantly after treatment (P < 0. 05).

CONCLUSIONThe level of PDGF-BB and mRNA is high in renal tissue of adriamycin-induced nephrotic rats. This progress could be effectively inhibited by Haikun Shenxi and the mechanism may be that it can control the excessive expression of PDGF-BB and mRNA.

Animals ; Blood Urea Nitrogen ; Creatinine ; blood ; Doxorubicin ; Drugs, Chinese Herbal ; chemistry ; isolation & purification ; pharmacology ; Gene Expression Regulation ; drug effects ; Glomerular Mesangium ; drug effects ; metabolism ; pathology ; Glomerulosclerosis, Focal Segmental ; chemically induced ; genetics ; metabolism ; Immunohistochemistry ; In Situ Hybridization ; Kidney ; drug effects ; metabolism ; pathology ; Male ; Medicine, Chinese Traditional ; Phaeophyta ; chemistry ; Platelet-Derived Growth Factor ; biosynthesis ; genetics ; Polysaccharides ; chemistry ; isolation & purification ; pharmacology ; Proto-Oncogene Proteins c-sis ; RNA, Messenger ; biosynthesis ; genetics ; Random Allocation ; Rats ; Rats, Wistar

OBJECTIVETo study the clinicopathologic features of membranous nephropathy coexisting with IgA nephropathy.

METHODSThe renal biopsies performed in Peking University First Hospital during the period from January, 1998 to April, 2006 were retrospectively reviewed. The clinicopathologic features of 11 cases of membranous nephropathy coexisting with IgA nephropathy were studied. Electron microscopy with immunogold labeling for IgG and IgA were also performed.

RESULTSThe mean age of patients was 39.9 years. The male-to-female ratio was 1:2.9. The patients mainly presented with proteinuria. Proteinuria of nephrotic level was seen in 7 cases (63.6%). Seven cases also had associated microscopic hematuria. None of them showed evidence of renal insufficiency. Cases with secondary diseases, such as hepatitis virus infection and systemic lupus erythematosus, were excluded from the study. Histologically, vacuolation and thickening of glomerular basement membrane was seen. There was also mild mesangial hypercellularity and increase in mesangial matrix. Occasional glomeruli with crescent formation were identified in 2 cases. Immunofluorescence study showed granular staining for IgG and C3 along glomerular capillary walls, in addition to clumps of IgA deposits in mesangium. Electron microscopy revealed subepithelial and mesangial electron-dense deposits. Immunogold labeling showed IgG and IgA localized in the subepithelial and mesangial deposits respectively.

CONCLUSIONMembranous nephropathy coexisting with IgA nephropathy possesses the clinicopathologic features of both components. It might be caused by independent occurrence of the two entities.

Adult ; Female ; Glomerular Basement Membrane ; immunology ; pathology ; ultrastructure ; Glomerular Mesangium ; immunology ; pathology ; ultrastructure ; Glomerulonephritis, IGA ; complications ; immunology ; pathology ; Glomerulonephritis, Membranous ; complications ; immunology ; pathology ; Humans ; Immunoglobulin A ; metabolism ; Immunoglobulin G ; metabolism ; Kidney Glomerulus ; immunology ; pathology ; ultrastructure ; Male ; Middle Aged ; Retrospective Studies

Diabetic nephropathy is characterized by an expansion of the glomerular mesangium, caused by mesangial cell proliferation and an excessive accumulation of extracellar matrix (ECM) proteins, which eventually leading to glomerulosclerosis. TGF-beta1 was found to play an important role in the accumulation of ECM in the kidney. In this study, TGF-beta1 RNA interference was used as an effective therapeutic strategy. The inhibitory effect of TGF-beta1 small interfering RNAs (siRNAs) on the high glucose-induced overexpression of TGF-beta1 in rat mesangial ceys (RMCs). A high levels of glucose induces TGF-beta1 mRNA and protein, and TGF-beta1 siRNAs reduce the ability of high glucose to stimulate their expression. We also examined the inhibitory effect of TGF-beta1 siRNAs on the expression of plasminogen activator inhibitor (PAI)-1 and Collagen Type I which are down-regulators of TGF-beta1. The expression of TGF-beta1, PAI-1 and Collagen Type I was increased in RMCs that were stimulated by 30 mM glucose. TGF-beta1 siRNAs reduces high glucose-induced TGF-beta1, PAI-1, and Collagen Type I mRNA and protein expression in a dose-dependent manner. In conclusion, the present study demonstrates that TGF-beta1 siRNAs effectively inhibits TGF-beta1 mRNA and protein expression in RMCs. These suggest that TGF-beta1 siRNAs through RNAi may be a useful tool for developing new therapeutic applications for the treatment of diabetic nephropathy.
Transforming Growth Factor beta1/*metabolism ; Rats, Sprague-Dawley ; Rats ; RNA, Small Interfering/*metabolism ; Microscopy, Fluorescence ; Mesangial Cells/*metabolism ; Male ; Glucose/*metabolism ; Glomerular Mesangium/*metabolism ; Gene Expression Regulation ; Diabetic Nephropathies/pathology ; Collagen Type I/metabolism ; Cells, Cultured ; Cell Proliferation ; Animals

OBJECTIVETo study the mechanism of Shenkangwan (SKW) in treating early diabetic nephropathy (DN).

METHODSThe effect of SKW on NO and transforming growth factor (TGF)-beta(1) production by the mesangial cells (MCs) of rats with early diabetic nephropathy was evaluated with serum pharmacological method.

RESULTSCompared with normal serum, the SKW-containing serum dose- and time-dependently inhibited TGF-beta(1) excretion and increased NO production in the MCs of rats with early DN (P<0.05 and P<0.01, respectively).

CONCLUSIONThe therapeutic effect of SKW on early DN may rely on the balance modulation of cytokine network by increasing NO production and decreasing TGF-beta(1) excretion to prevent cytokine-induced damage of the MCs.

Animals ; Diabetes Mellitus, Experimental ; drug therapy ; metabolism ; Diabetic Nephropathies ; drug therapy ; metabolism ; Drugs, Chinese Herbal ; therapeutic use ; Glomerular Mesangium ; metabolism ; pathology ; Male ; Nitric Oxide ; biosynthesis ; Rats ; Rats, Wistar ; Transforming Growth Factor beta ; biosynthesis

Here we report two cases of isolated diffuse mesangial sclerosis (IDMS) with early onset end-stage renal failure. These female patients did not show abnormalities of the gonads or external genitalia. Direct sequencing of WT1 PCR products from genomic DNA identified WT1 mutations in exons 8 (366 Arg>His) and 9 (396 Asp>Tyr). These mutations have been reported previously in association with Denys-Drash syndrome (DDS) with early onset renal failure. Therefore we suggest that, at least in part, IDMS is a variant of DDS and that investigations for the WT1 mutations should be performed in IDMS patients. In cases with identified WT1 mutations, the same attention to tumor development should be required as in DDS patients, and karyotyping and serial abdominal ultrasonograms to evaluate the gonads and kidney are warranted.
Base Sequence ; DNA/chemistry/genetics ; DNA Mutational Analysis ; Fatal Outcome ; Female ; Glomerular Mesangium/*pathology ; Humans ; Infant ; Infant, Newborn ; *Mutation ; Nephrosclerosis/*genetics ; WT1 Proteins/*genetics

BACKGROUND: Transforming growth factor-beta (TGF-beta) stimulates renal fibrosis in various renal diseases including IgA nephropathy. METHODS: We examined whether immunoglobulin A (IgA) stimulated TGF-beta1 synthesis in human mesangial cells (MCs), and whether this effect was mediated through the protein kinase C (PKC) pathway. We measured the intraglomerular TGF-beta1 mRNA expression by using competitive RT-PCR, and this was compared with various parameters in IgA nephropathy patients. RESULTS: The IgA aggregate increased the TGF-beta1 mRNA expression in MCs, while this expression was not affected by the culture media or IgG aggregate. Phorbol 12-myristate 13-acetate and calphostin C did not influence the TGF-beta1 mRNA expression that was increased by the IgA aggregate. Intraglomerular TGF-beta1 mRNA expression was significantly correlated with creatinine clearance (r=-0.764, p=0.027), daily proteinuria (r=0.781, p=0.022), serum creatinine (r=0.884, p=0.004), and tubulointerstitial changes (r=0.809, p=0.015). Glomerular TGF-beta1 mRNA expression was associated with an increased tendency for glomerulosclerosis (r=0.646, p=0.084). After 4 years, patients with a high expression of intraglomerular TGF-beta1 mRNA showed a tendency for an decrease of their renal function. CONCLUSION: The IgA aggregate increased TGF-beta1 mRNA expression in MCs, and this was independent of the PKC pathway. The evaluation of intraglomerular TGF-beta1 mRNA expression could be useful in predicting the progression of IgA nephropathy.
Cells, Cultured ; Female ; Glomerular Mesangium/*cytology/metabolism ; Glomerulonephritis, IGA/metabolism/pathology ; Humans ; Immunoglobulin A/*pharmacology ; Male ; Proteins/*metabolism ; RNA, Messenger/*metabolism ; Research Support, Non-U.S. Gov't