Nefropatía por inmunoglobulina M: características histopatológicas y clínicas. Serie de casos / Immunoglobulin M nephropathy: histopathological and clinical characteristics. Case series

La nefropatía por inmunoglobulina M (NIgM) es una glomerulopatía idiopática caracterizada por depósitos mesangiales globales y difusos de IgM. Se realizó un estudio retrospectivo de las características clínicas e histopatológicas de los pacientes con NIgM atendidos en nuestro servicio. De 241 biopsias renales, 21 correspondieron a NIgM (8,7 %). Se incluyeron 18 pacientes (14 de sexo femenino, mediana de edad: 3,08 años). Se excluyó a 1 paciente por enfermedad sistémica asociada y a 2 por seguimiento menor a 1 año. Catorce pacientes se manifestaron con síndrome nefrótico (SN) y 4 con proteinuria aislada o asociada a hematuria. En la microscopia óptica, 13 presentaron hiperplasia mesangial, y 5 esclerosis focal y segmentaria. De los pacientes con SN, 7 fueron corticorresistentes, 4 corticodependientes y 3 presentaban recaídas frecuentes. Todos los pacientes con SN y 1 con proteinuria-hematuria recibieron inmunosupresores; los 18 pacientes recibieron, además, antiproteinúricos. Luego de 5,2 años (2-17,5) de seguimiento, 6 pacientes evolucionaron a enfermedad renal crónica

Immunoglobulin M nephropathy (IgMN) is an idiopathic glomerulopathy characterized by diffuse global mesangial deposits of IgM. We retrospectively studied the clinical and histopathological characteristics of the patients with IgMN seen in our service. Of 241 renal biopsies, 21 corresponded to IgMN (8.7 %). One patient was excluded due to associated systemic disease and 2 due to follow-up less than 1 year, 18 were included (14 girls, median age 3.08 years). Fourteen manifested with nephrotic syndrome (NS) and the remaining with proteinuria (isolated or associated with hematuria). On light microscopy, 13 had hyperplasia with mesangial expansion and 5 had focal and segmental sclerosis. Of the patients with NS, 7 were steroid-resistant, 4 steroid-dependent, and 3 frequent relapsers. All patients with NS and 1 with proteinuria-hematuria received immunosuppressants; the 18 patients also received antiproteinuric drugs. After 5.2 years (2-17.5) of follow-up, 6 patients developed chronic kidney disease.

[Immunoglobulin M nephropathy: histopathological and clinical characteristics. Case series]. / Nefropatía por inmunoglobulina M: características histopatológicas y clínicas. Serie de casos.

Immunoglobulin M nephropathy (IgMN) is an idiopathic glomerulopathy characterized by diffuse global mesangial deposits of IgM. We retrospectively studied the clinical and histopathological characteristics of the patients with IgMN seen in our service. Of 241 renal biopsies, 21 corresponded to IgMN (8.7 %). One patient was excluded due to associated systemic disease and 2 due to follow-up less than 1 year, 18 were included (14 girls, median age 3.08 years). Fourteen manifested with nephrotic syndrome (NS) and the remaining with proteinuria (isolated or associated with hematuria). On Nefropatía por inmunoglobulina M: características histopatológicas y clínicas. Serie de casos Immunoglobulin M nephropathy: histopathological and clinical characteristics. Case series light microscopy, 13 had hyperplasia with mesangial expansion and 5 had focal and segmental sclerosis. Of the patients with NS, 7 were steroid-resistant, 4 steroid-dependent, and 3 frequent relapsers. All patients with NS and 1 with proteinuria-hematuria received immunosuppressants; the 18 patients also received antiproteinuric drugs. After 5.2 years (2-17.5) of follow-up, 6 patients developed chronic kidney disease.

La nefropatía por inmunoglobulina M (NIgM) es una glomerulopatía idiopática caracterizada por depósitos mesangiales globales y difusos de IgM. Se realizó un estudio retrospectivo de las características clínicas e histopatológicas de los pacientes con NIgM atendidos en nuestro servicio. De 241 biopsias renales, 21 correspondieron a NIgM (8,7 %). Se incluyeron 18 pacientes (14 de sexo femenino, mediana de edad: 3,08 años). Se excluyó a 1 paciente por enfermedad sistémica asociada y a 2 por seguimiento menor a 1 año. Catorce pacientes se manifestaron con síndrome nefrótico (SN) y 4 con proteinuria aislada o asociada a hematuria. En la microscopia óptica, 13 presentaron hiperplasia mesangial, y 5 esclerosis focal y segmentaria. De los pacientes con SN, 7 fueron corticorresistentes, 4 corticodependientes y 3 presentaban recaídas frecuentes. Todos los pacientes con SN y 1 con proteinuria-hematuria recibieron inmunosupresores; los 18 pacientes recibieron, además, antiproteinúricos. Luego de 5,2 años (2-17,5) de seguimiento, 6 pacientes evolucionaron a enfermedad renal crónica.

JAK-STAT Activity in Peripheral Blood Cells and Kidney Tissue in IgA Nephropathy.

BACKGROUND AND OBJECTIVES: IgA nephropathy is the most common primary glomerular disease in the world. Marked by mesangial inflammation and proliferation, it generally leads to progressive kidney fibrosis. As the Janus kinase signal transducer and activator of transcription pathway has been implicated as an important mediator of diabetic kidney disease and FSGS, detailed investigation of this pathway in IgA nephropathy was undertaken to establish the basis for targeting this pathway across glomerular diseases. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Well characterized patients with IgA nephropathy and controls were studied, allowing us to compare 77 patients with biopsy-proven IgA nephropathy with 45 healthy subjects. STAT phosphorylation was assessed in peripheral blood monocytes (PBMCs) by phosphoflow before and after cytokine stimulation. Kidney Janus kinase signal transducer and activator of transcription activity was studied by immunofluorescence and by transcriptomic studies. An STAT1 activity score was established using downstream transcriptional targets of pSTAT1 and associated with disease and clinical outcomes. RESULTS: We found PBMCs to have upregulated pSTAT production at baseline in patients with IgA nephropathy with a limited reserve to respond to cytokine stimulation compared with controls. Increased staining in glomerular mesangium and endothelium was seen for Jak-2 and pSTAT1 and in the tubulointerstitial for JAK2, pSTAT1, and pSTAT3. Activation of the Janus kinase signal transducer and activator of transcription pathway was further supported by increased pSTAT1 and pSTAT3 scores in glomerular and tubulointerstitial sections of the kidney (glomerular activation Z scores: 7.1 and 4.5, respectively; P values: <0.001 and <0.001, respectively). Clinically, phosphoflow results associated with proteinuria and kidney function, and STAT1 activation associated with proteinuria but was not associated with progression. CONCLUSIONS: Janus kinase signal transducer and activator of transcription signaling was activated in patients with IgA nephropathy compared with controls. There were altered responses in peripheral immune cells and increased message and activated proteins in the kidney. These changes variably related to proteinuria and kidney function.

The Role of Immune Modulation in Pathogenesis of IgA Nephropathy.

IgA nephropathy (IgAN) is the most prevalent primary glomerulonephritis worldwide, with diverse clinical manifestations characterized by recurrent gross hematuria or microscopic hematuria, and pathological changes featuring poorly O-galactosylated IgA1 deposition in the glomerular mesangium. Pathogenesis has always been the focus of IgAN studies. After 50 years of research, most scholars agree that IgAN is a group of clinicopathological syndromes with certain common immunopathological characteristics, and multiple mechanisms are involved in its pathogenesis, including immunology, genetics, and environmental or nutritional factors. However, the precise pathogenetic mechanisms have not been fully determined. One hypothesis about the pathogenesis of IgAN suggests that immunological factors are engaged in all aspects of IgAN development and play a critical role. A variety of immune cells (e.g., dendritic cells, NK cells, macrophages, T-lymphocyte subsets, and B-lymphocytes, etc.) and molecules (e.g., IgA receptors, Toll-like receptors, complements, etc.) in innate and adaptive immunity are involved in the pathogenesis of IgAN. Moreover, the abnormality of mucosal immune regulation is the core of IgAN immunopathogenesis. The roles of tonsil immunity or intestinal mucosal immunity, which have received more attention in recent years, are supported by mounting evidence. In this review, we will explore the latest research insights on the role of immune modulation in the pathogenesis of IgAN. With a better understanding of immunopathogenesis of IgAN, emerging therapies will soon become realized.

Mesangial C4d Deposits in Early IgA Nephropathy.

BACKGROUND AND OBJECTIVES: The prognostic value of mesangial C4d deposits in IgA nephropathy has been analyzed in patients with reduced GFR but has not been analyzed in those with normal kidney function. The main objective of the study was to analyze the prognostic value of C4d deposits and association with response to treatment in patients with IgA nephropathy and normal GFR. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This retrospective cohort study included 190 patients with idiopathic IgA nephropathy diagnosed by kidney biopsy between 1988 and 2005. The patients had GFR≥80 ml/min per 1.73 m2 at the time of diagnosis, and they had a paraffin-embedded kidney biopsy with eight glomeruli available. RESULTS: In total, 170 (89%) and 20 (11%) patients were >18 and <18 years old, respectively; median (interquartile range) follow-up was 15 (12-22) years. Mesangial C4d deposit prevalence was 20% (38 of 190). At diagnosis, C4d-positive versus -negative patients had higher protein-to-creatinine ratio (median [interquartile range]: 1.94 g/g [0.9-3.1] versus 1.45 g/g [0.9-2.2]; P=0.04). During follow-up, C4d-positive patients showed a higher number of nephritic flares (median [range]: 1.4 [0-5] versus 0.9 [0-2]; P=0.04), had a higher protein-to-creatinine ratio (median [interquartile range]: 1.32 g/g [0.7-1.7] versus 0.89 g/g [0.1-1.3]; P<0.01), were more prone to receive repeated treatment with corticosteroids (45% versus 24%; P<0.01), and showed a larger reduction in eGFR (-1.6 versus -0.8 ml/min per 1.73 m2 per year; P=0.04). Furthermore, the presence of mesangial C4d deposits was an independent predictor of long-term kidney survival. CONCLUSIONS: C4d deposits may be one of the earliest poor prognostic variables available for patients with idiopathic IgA nephropathy and normal kidney function at the time of diagnosis. However, Cd4 deposits alone are not associated with the response to angiotensin blockers or corticosteroid treatment.

Restricted nutrition-induced low birth weight, low number of nephrons and glomerular mesangium injury in Japanese quail.

Insufficient nutrition during the perinatal period causes structural alterations in humans and experimental animals, leading to increased vulnerability to diseases in later life. Japanese quail, Coturnix japonica, in which partial (8-10%) egg white was withdrawn (EwW) from eggs before incubation had lower birth weights than controls (CTs). EwW birds also had reduced hatching rates, smaller glomeruli and lower embryo weight. In EwW embryos, the surface condensate area containing mesenchymal cells was larger, suggesting that delayed but active nephrogenesis takes place. In mature EwW quail, the number of glomeruli in the cortical region (mm2) was significantly lower (CT 34.7±1.4, EwW 21.0±1.2); capillary loops showed focal ballooning, and mesangial areas were distinctly expanded. Immunoreactive cell junction proteins, N-cadherin and podocin, and slit diaphragms were clearly seen. With aging, the mesangial area and glomerular size continued to increase and were significantly larger in EwW quail, suggesting compensatory hypertrophy. Furthermore, apoptosis measured by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling analysis was higher in EwWs than in CTs on embryonic day 15 and postnatal day 4 (D4). Similarly, plasma glucocorticoid (corticosterone) was higher (P<0.01) on D4 in EwW quail. These results suggest that although nephrogenic activity is high in low-nutrition quail during the perinatal period, delayed development and increased apoptosis may result in a lower number of mature nephrons. Damaged or incompletely mature mesangium may trigger glomerular injury, leading in later life to nephrosclerosis. The present study shows that birds serve as a model for 'fetal programming,' which appears to have evolved phylogenetically early.

CagA promotes proliferation and secretion of extracellular matrix by inhibiting signaling pathway of apoptosis in rat glomerular mesangial cells.

Cytotoxin-associated antigen A (CagA), a major virulence factor of Helicobacter pylori (Hp), is associated with the pathogenesis of peptic ulcer and gastric cancer. Recent researches demonstrated that Hp exists in palatine tonsil in all studied IgA nephropathy (IgAN) patients, most of which were CagA-positive, suggesting that CagA may be a causative pathogenic factor of IgAN. However, the underlying molecular mechanisms and signaling pathway are still largely unclear. In the present study, CCK8 assay, enzyme-linked immunosorbent assay, and immunohistochemistry were performed to investigate the effect of CagA on cell proliferation and extracellular matrix secretion in rat glomerular mesangial cells. RT-PCR and western blotting were used to reveal the potential signaling pathway. Rat glomerular mesangial cells were treated with recombinant CagA protein for 72 h, in a dose- and time-dependent manner. We found that CagA promoted cell proliferation and extracellular matrix secretion by inhibiting signaling pathway of apoptosis. Taken together, these findings suggested that CagA induced cellular injury in glomerular mesangium by proliferation and secretion of extracellular matrix, and may play an important role in pathogenesis of IgAN.

Renal stromal miRNAs are required for normal nephrogenesis and glomerular mesangial survival.

MicroRNAs are small noncoding RNAs that post-transcriptionally regulate mRNA levels. While previous studies have demonstrated that miRNAs are indispensable in the nephron progenitor and ureteric bud lineage, little is understood about stromal miRNAs during kidney development. The renal stroma (marked by expression of FoxD1) gives rise to the renal interstitium, a subset of peritubular capillaries, and multiple supportive vascular cell types including pericytes and the glomerular mesangium. In this study, we generated FoxD1(GC);Dicer(fl/fl) transgenic mice that lack miRNA biogenesis in the FoxD1 lineage. Loss of Dicer activity resulted in multifaceted renal anomalies including perturbed nephrogenesis, expansion of nephron progenitors, decreased renin-expressing cells, fewer smooth muscle afferent arterioles, and progressive mesangial cell loss in mature glomeruli. Although the initial lineage specification of FoxD1(+) stroma was not perturbed, both the glomerular mesangium and renal interstitium exhibited ectopic apoptosis, which was associated with increased expression of Bcl2l11 (Bim) and p53 effector genes (Bax, Trp53inp1, Jun, Cdkn1a, Mmp2, and Arid3a). Using a combination of high-throughput miRNA profiling of the FoxD1(+)-derived cells and mRNA profiling of differentially expressed transcripts in FoxD1(GC);Dicer(fl/fl) kidneys, at least 72 miRNA:mRNA target interactions were identified to be suppressive of the apoptotic program. Together, the results support an indispensable role for stromal miRNAs in the regulation of apoptosis during kidney development.

Tbx18 is essential for normal development of vasculature network and glomerular mesangium in the mammalian kidney.

Tbx18 has been shown to be essential for ureteral development. However, it remains unclear whether it plays a direct role in kidney development. Here we addressed this by focusing on examining the pattern and contribution of Tbx18+ cells in the kidney and its role in kidney vascular development. Expression studies and genetic lineage tracing revealed that Tbx18 is expressed in renal capsule, vascular smooth muscle cells and pericytes and glomerular mesangial cells in the kidney and that Tbx18-expressing progenitors contribute to these cell types. Examination of Tbx18(-/-) kidneys revealed large reduction in vasculature density and dilation of glomerular capillary loops. While SMA+ cells were reduced in the mutant, PDGFRß+ cells were seen in early capillary loop renal corpuscles in the mutant, but fewer than in the controls, and further development of the mesangium failed. Analysis of kidney explants cultured from E12.5 excluded the possibility that the defects observed in the mutant were caused by ureter obstruction. Reduced proliferation in glomerular tuft and increased apoptosis in perivascular mesenchyme were observed in Tbx18(-/-) kidneys. Thus, our analyses have identified a novel role of Tbx18 in kidney vasculature development.

Enhanced calcium release induced by tumor necrosis factor alpha in glomerular mesangial cells participated in hepatorenal syndrome / 中国医师杂志

Objective To investigate the effect of tumor necrosis factor-α (TNF-α) on intracellular calcium concentration ([Ca2 +] i) and the contraction of glomerular mesangial cells (GMCs),and prove that hypercontractility of GMCs induced by TNF-α in hepatorenal syndrome(HRS) was connected with inositol 1,4,5-trisphophate receptors (IP3Rs).Methods GMCs were divided into TNF-α-treated 0 h,4h,and 24 h groups.Another 3 groups were blocked by 2-APB.The effect of TNF-α on [Ca2 +] i was identified and observed whether it could be blocked by 2-APB.Contraction of GMCs was determined by accessing the surface area of cells before and after contraction.Results TNF-α significantly increased ET-induced calcium release,in that we found higher [Ca2 +] i after stimulated by ET in TNF-α-treated 4 h group and 24 h group[4 h:(648.08 ±267.11) nmol/L; 24 h:(879.30 ±-260.29) nmol/L; 0 h:(619.93 ±258.94)nmol/L,F =5.486,4 h vs 0 h:P ＜ 0.05 ; 24 h vs 0 h:P ＜ 0.05 ;24 h vs 4 h:P ＞ 0.05].This phenomenon can be totally blocked by 2-APB in all groups.The change in planar surface area in response to ET was slightly in control cells but significantly enhanced in TNF-α-treated cells [4 h:(2198 ± 340)μm2; 24h:(2260±553)μm2; 0 h:(2436±474)μm2,F =4.001,4 h vs0 h:P ＜0.05; 24 h vs0 h:P ＜0.05;24 h vs 4 h:P ＞ 0.05].Conclusion TNF-α can enhance ET-induced sarcoplasmic reticulum Ca2 + release and increase the contractile responses of GMCs to ET,which is associated with IP3Rs.TNF-α is responsible for hyperconstractility of glomeruli in HRS.

Effect of angiotensin-(1-7) on proliferation and secretion of cultured rat's glomerular mesangial cells induced by transforming growth factor-β1 / 中国医师杂志

Objective To explore the effect of angiotensin-(1-7) [Ang-(1-7)] on proliferation and secretion in cultured rat's glo-merular mesangial cells(GMC) induced by transforming growth factor-β1 (TGF-β1). Methods GMC in logarithmic growth phase were in-cubated, and then were divided into 4 groups: control, Ang-(1-7), TGF-β1,and TGF-β1 + Ang-(1-7) group. Cell numbers of rat's GMC were detected by WST-1. Laminin(LN) and collagenlV (ColⅣ) mRNA expressions in GMC were analyzed by RT-PCR. The secretion of LN and ColⅣ in culture medium of rat's GMC was measured by radioimmunoassay. Results Ang-(1-7) significantly inhibited basal and TGF-β1-induced proliferation of cultured glomerular mesangial cells. Ang-(1-7) significantly down-regulated LN and Col Ⅳ mRNA expressions in glomerular mesangial cells and also inhibited the secretion of LN and ColⅣ induced by TGF-β1(P <0. 05). Conclusions Ang-(1-7) can inhibit basal and TGF-β1-induced proliferation, and inhibit ECM secretion of cultured rats glomerular mesangial cells.

The effect of the interaction of mesangial cells and endothelial cells on diabetic nephropathy / 中国医师杂志

Objective To study the effect of high glucose and lysophosphatidylcholine (LPC) on the role of fibronectin and plate-let activating factor (PAF) via the interaction of endothelial cells and mesangial cells. Methods The model of intercellular interaction be-tween endothelial cells and mesangial cells was established and divided into 4 groups: control, mannitol, high glucose and LPC, and BN52021 group. The level of fibronectin and PAF were determined by enzyme linked immunosorbent assay in the culture media. Results The level of fibronectin and PAF of high glucose and LPC group were higher than those of control group in co-culture and monolayer cell cul-ture (P<0.05). Intervened by high glucose and LPC, the level of fibronectin and PAF of co-culture were higher than those from monolay-er cell culture (P<0.05). The level of fibrocentin in the BN52021 group was lower than that of high glucose and LPC (P<0.05). Con-clusions Exposed to high glucose and LPC, endothelial cells and mesangial cells can interact with each other to produce more fibrocentin and PAF. The increase of fibronectin is partly concerned with PAF.

Effect of high glucose on the role of fibronectin, collagen Ⅳ and platelet activating factor of mesangial cells / 中国医师杂志

promoted by high glucose, which can enlarge the biological effect of PAF.

Effects of keto-valine-calcium and keto-isoleucine-calcium on proliferation of human mesangial cells and its mechanism study / 中国医师杂志

Objective To study the effects of keto-valine-calcium and keto-isoleucine-calcium on(human mesangial cells)HMCs. Method HMCs were stimulated by keto-valine-calcium and keto-isoleucine-calcium. The AT1R and TGF-β1 were detected. MTr method was used to measure the proliferation of HMCs, and cell cycle was studied by flow cytometry. Results The expression of AT1R and TGF-β1was increased in the experiment groups compared with negative and DMSO control groups. Cell cycle G1 attest and cell apoptosis were observed in the experiment groups. Conclusions 10mM keto-valine-calcium and keto-isoleueine-calcium have multiple effects on HMCs in vitro, which not only increased the expression of AT1R,but also the expression of TGF-β1.Furthermore,keto-valine-calcium and keto-isoleucine-calcium can induce cell cycle G1 arrest and cell apoptosis.

Regulation of intercellular adhesion molecule-1 expression in murine glomerular mesangial cells by lipoprotein(a) / 中国医师杂志

Objective To investigate the effects of Lp(a)on proliferation GMCs of rat model induced by lipopolysaccharide and explore the possible mechanism of Lp(a)in the proliferation of rat GMCs.Methods To observe the effects of Lp(a)on proliferation of GMCs,different dosage of Lp(a)were used,The research were divided into three groups:Control group,LPS group,Lp(a)group.After culture(at the end of 12h,24h,48h,60h and 72h),the cultured GMCs and suspension were collected to observe the rate of GMCs proliferation by MTT,the positive rate of proliferation cell nuclear antigen(PCNA)by immunohistochemisty,and the level of intercellular adhesion molecule-1(ICAM-1)by ELISA respectively.Results Compared with control and LPS group,MTT,positive rate of PCNA and ICAM-1 of GMCs were increased more significantly in Lp(a)group.MTT ,the positive rate of PCNA and ICAM-1 of GMCs were increased as Lp(a)dosage increased,a maximal effect was seen when Lp(a)was 2.5 μg/L or 5.0μg/L.When the dosage continue increased,MTT,the positive rate of PCNA and ICAM-1 activity of GMCs began to decrease in Lp(a)group.ICAM-1 showed positive correlation with MTT and the positive rate of PCNA.Conclusion Lp(a)can significantly affect the rate of GMCs proliferation,and this affection is in a dosage-and timedependent manner.Low dosage stimulates GMCs proliferation, and high dosage inhibits GMCs proliferation.ICAM-1 shows positive correlation with MTT and the positive rate of PCNA.The effect of Lp(a)on GMCs may be through ICAM-1.

The extracellular calcium sensing receptor is expressed in mouse mesangial cells and modulates cell proliferation

The extracellular calcium sensing receptor (CaSR) belongs to the type III family of G-protein-coupled receptors, a family that comprises the metabotropic glutamate receptor and the putative vomeronasal organ receptors. The CaSR plays an important role for calcium homeostasis in parathyroid cells, kidney cells and other cells to directly 'sense' changes in the extracellular calcium ion concentration ((Ca2+)o). The mesangial cells are known to be involved in many pathologic sequences through the mediation of altered glomerular hemodynamics, cell proliferation, and matrix production. In this study, we examined the expression of the CaSR in the mouse mesangial cell lines (MMC, ATCC number CRL-1927). Reverse transcription- polymerase chain reaction (RT-PCR) was perform with CaSR-specific primers, and this was followed by nucleotide sequencing of the amplified product; this process identified the CaSR transcript in the MMCs. Moreover, CaSR protein was present in the MMCs as assessed by Western blot and immunocytochemical analysis using a polyclonal antibody specific for the CaSR. Functionally, (Ca2+)o induced the increment of the intracellular calcium concentration ((Ca2+)i) in a dose-dependent manner. This (Ca2+)i increment by (Ca2+)o was attenuated by the pretreatment with a phospholipase C inhibitor (U73122) and also by a pretreatment with a CaSR antagonist (NPS 2390). The similar results were also obtained in IP3 accumulation by (Ca2+)o. To investigate the physiological effect of the CaSR, the effect of the (Ca2+)o on cell proliferation was studied. The increased (Ca2+)o (up to 10 mM) produced a significant increase in the cell numbers. This mitogenic effect of (Ca2+)o was inhibited by the co-treatment with a CaSR antagonist. From these results, the (Ca2+)o-induced (Ca2+)i elevation in the MMC is coupled with the extracellular calcium sensing receptor. Furthermore, (Ca2+)o produces a mitogenic effect in MMCs.

The distribution and clinical significance of IgG subclasses of anti-glomerular basement membrane antibodies / 北京大学学报(医学版)

Objective: It was reported that major subclasses of anti-golmerular basement membrane (GBM) antibody were IgG1 and IgG4. The IgG1 subclass was mainly found in male patients and IgG4 subclass in female patients with anti-GBM disease. This study investigates the distribution of anti-GBM IgG subclasses and their association with clinical characteristics. Methods: Sera from 50 patients diagnosed as anti-GBM disease during 1991-2003 were collected. The anti-GBM antibodies with IgG1, IgG2, IgG3, and IgG4 subclasses were detected with purified bovine ?(IV)NC1 as solid phase ligand in ELISA. The association with clinical manifestations was further investigated. Results: The positive rates of IgG anti-GBM subclasses were IgG1 94%, IgG2 56%, IgG3 12%, IgG4 88%, respectively. IgG1 and IgG4 were the main subclasses in anti-GBM IgG subclasses (P

Pathologic Changes on Glomerulic Area in Non-Dependent Diabetes Mellitus(Type 2 DM) Patients / 中国医师杂志

Objeetive To explore the relationship among the glomerular mesangium components,degree of renal lesion and glomerulosclerosis in patients with type 2 DM.Method A quantitative study of type Ⅳ collagen in kidneys taken from twenty-one patients with type 2 DM and ten-two control autoptical renal tissue specimens were investigated by immunochemical techniques,computer image analysis system.Results The amounts of type Ⅳ collagen were increased parallel with advances of glomerulosclerosis and renal arteriolosclerosis in patients with type 2 DM,but the collagen had not obviously elevation in renal failure patients.Conclusions The increased type Ⅳ collagen is a characteristic manifestation of early and moderate lesions of glomerulosclerosis in type 2 DM.Quantitative determination of glomerular mesangium components could be a good index to judge the lesion degree of kidney.

Mechanisms of nitric oxide synthesis induced by human complement C5b-9complex in glomerular mesangial cells of rats / 中国病理生理杂志

AIM: To explore the mechanism of the nitric oxide (NO) synthesis induced by human C5b-9 complex in glomerular mesangial cells(MC) of rats. METHODS: The MC of rats were cultured and stimulated with human complement C5b-9 complex to induce TNF? and IL-1?. At the same time, several parameters related to NO synthesis were measured at 3 h, 6 h and 24 h after C5b-9 stimulation. The effects of monoclonal antibodies against TNF? and IL-1? on NO synthesis were examined in this system. RESULTS: TNF? concentration in supernatant from MC in C5b-9 group was higher than that of control group at 6, 24 h after stimulation with C5b-9 complex and reversed by adding anti-TNF? McAb. C5b-9 complex didn't stimulate the release of IL-1? in same system. In addition, the expression of iNOS mRNA in MC was observed at 3 h after stimulation with C5b-9. Levels of iNOS mRNA expression and cGMP in MC and NO - 3/NO - 2 in supernatant from MC in C5b-9 group were higher than those in control group at 6, 24 h after C5b-9 stimulation, these changes were also reversed by adding monoclonal antibody against TNF?. CONCLUSION: C5b-9 complex could induce iNOS mRNA expression at 3 h after C5b-9 stimulation, and the synthesis of NO at 6, 24 h was related to TNF? released from cultured MC of rats by C5b-9 complex to a certain extent.

Effects of lipopolysaccharide and interleukin 1 receptor antagonist on proliferation and nitric oxide synthesis of mesangial cells / 中国病理生理杂志

AIM: To investigate the effects of Lipopolysaccharide(LPS) and interleukin 1 receptor antagonist(IL-1ra) on mesangial cells proliferation and nitric oxide synthesis. METHODS: Glomerular mesangial cells from SD rats were cultured. The first and second passages of cultured cells were used for the experiment. LPS and LPS plus IL-1ra were added in cell cultures, respectively. By using chemical method the nitrite in supernatants was measured,3H-TdR incorporation was determined to evaluate the GMC proliferation. Northern and slot hybridizations were performed to detect the expression of iNOS mRNA. RESULTS: There were expression of iNOS mRNA, more production of nitrite(0.64?0.25 vs 0.12?0.06 nmol/104 cell) in supernatants and GMC proliferation(3735?1177.9 vs 1785?280.6) in LPS group compared to the control. While compared with LPS group, in LPS+IL-1ra GMC group, expression of iNOS mRNA decreased by 40%, nitrite increased(3.28?0.33 nmol/104 cell), proliferation of GMC decreased (818?77.27). CONCLUSION: LPS could activate the GMC to express iNOS mRNA and produce more nitrite. IL-1ra could partially inhibit the effects of LPS on the expression of iNOS mRNA in GMC, but not nitrite. There is no synchronous correlation between NO production and GMC proliferation.