Effects of Fetal and Neonatal Murine Peripheral Blood Mononuclear Cells Infusion on MicroRNA-145 Expression in Renal Vascular Smooth Muscle Cells in MRL/lpr Mice.

For patients with refractory systemic lupus erythematosus, current medications are insufficient to control their condition, and new treatments are necessary. We aimed to evaluate the therapeutic effect of fetal and neonatal murine peripheral blood (FNPB) mononuclear cells and their impact on microRNA-145 (miR-145) in renal vascular smooth muscle cells (VSMCs) of MRL/lpr lupus-prone mice. MRL/lpr mice aged 20 weeks were randomized to 3 groups of 15 (control group, radiation group, infusion group). The renal tissues were subjected to pathological examination. In situ hybridization assay was applied to measure miR-145 expression in renal vessels of MRL/lpr mice. The infusion group had significantly better results for pathological renal tissue lesions than either the control or radiation group. In MRL/lpr mice, there was positive expression of miR-145 in renal VSMCs, although the expression of miR-145 was not discernible in renal vascular intima and adventitia. The miR-145 expression in renal VSMCs in the infusion group was significantly higher than in the control or radiation group, and higher in the radiation group than in the control group; however, the difference was not statistically significant. The increased expression of miR-145 in renal VSMCs might be one of the mechanisms supporting FNPB as a therapy for lupus nephritis; it also suggests that the miR-145 in renal vessels might be a new target for treatment of lupus nephritis.

[Relationship between serum thyroid hormone and GH-IGF axis, growth failure in nephrotic rats].

OBJECTIVE: To investigate the individual effects of malnutrition, nephrosis and glucocorticoid therapy on serum thyroid hormone, and explore the relationship between serum thyroid hormone and GH-IGF axis, growth failure in nephrotic rats. METHODS: Twenty-four male Sprague-Dawley (SD) rats were randomly divided into control group, pair-fed group, doxorubincin-induced nephrotic group (nephrotic group) and dexamethasone-treated nephrotic group (des-treated group). Serum T3/T4, GH and IGF-I were measured by RIA, serum IGFBPs were measured by Western ligand blot, liver GHR and IGF-I/IGFBPs mRNA were analyzed by radio-receptor assay and RT-PCR respectively. RESULTS: 1. Serum thyroid hormone was low in pair-fed group, lower in nephrotic group and lowest in des-treated group except for high serum T4 in pair-fed group. 2. Serum thyroid hormone was positively related with liver GHR, IGF-I/IGFBP-3 mRNA and serum IGF-I/IGFBP-3, and negatively related with serum IGFBP-2. 3. Serum thyroid hormone was positively related with nose-tail length and weight (both P < 0.01). CONCLUSIONS: The hypothyroidism is a possible mechanism of reducing serum IGF-I levels and biologic action, and resulting in growth failure in nephrotic syndrome.

[A quantitative analysis of renal pathology in the children with anaphylactoid purpura nephritis (APN)].

OBJECTIVE: To provide the theoretical value for the treatment and prognostic judgement of APN. METHODS: All cases were scored on the pathologic change of glomeruli and tubules. RESULTS: The pathologic scores of glomeruli in 30 cases were as follows: no one on Grade 0; 6(20%) on Grade 1; 17(56.7%) on Grade 2 and 7 (23.3%) on Grade 3. The pathologic scores of tubule were: Grade 0 was 2(6.7%); Grade 1 was 6(20%); Grade 2 was 14(46.7%); Grade 3 was 8(26.7%). There was positive correlation between glomerulus and tubule pathologic degree(r = 0.783, P < 0.01). The pathologic score of nephrotic syndrome in clinical manifestation was higher than that of non-nephrotic syndrome(P < 0.01). There was no significant difference in glomerular pathologic score between the simple urinary protein group and acute glomerulonephritis(AGN) group(P > 0.05), but tubular pathologic score in simple urinary proteins group was higher than that of AGN and essential hematuria group (P < 0.01, P < 0.05). The pathologic score of kidney(including glomerulus and tubule) was positively correlated with the disease course(r = 0.563, P < 0.01), but not with serum urea nitrogen and creatinine(r = 0.281, r = 0.236, P > 0.05). CONCLUSION: Serious tubular pathologic changes(not only glomerular pathologic change, but also tubular pathologic change in the APN children) were found in the patients with nephrotic syndrome and simple urinary proteins. Long-term urinary protein and the recurrence of the disease may be the important risk factor in kidney pathologic of APN.

[Effect of thrombin on cell proliferation and plasminogen activator inhibitor type (PAI-1) expression in human embryonic glomerular mesangial cells].

OBJECTIVE: To explore the effect of thrombin on cell proliferation and plasminogen-activator inhibitor Type 1(PAI-1) expression in human embryonic glomerular mesangial cells. METHODS: Methyl-tetragolium (MTT) incorporation, fibrin plate assay and Northern blotting hybridization were used to examine the mesangial cells proliferation, protein activity and mRNA expression of PAI-1 in cultured human embryonic mesangial cells induced by thrombin, respectively. RESULTS: Thrombin enhanced glomerular mesangial cell proliferation, PAI-1 protein activity and mRNA expression in a dose-dependent manner, which could be blocked by hirudin, a specific inhibitor of thrombin. CONCLUSION: Thrombin could enhance mesangial cell proliferation, and up-regulate protein activity and mRNA expression of PAI-1 in cultured human embryonic glomerular mesangial cells. It may play an important role in the pathogenesis of glomerulosclerosis induced by thrombin.

Rat macrophages in experimental IgA nephropathy.

To test whether the peripheral macrophage functions as early index of oxygen free radical release in association with the development of IgA nephropathy (IgAN), we studied female Lewis rats. IgAN was produced by treatment over 8 weeks with 0.1% bovine gamma globulin (BGG) in drinking water, followed by three daily intravenous injections of BGG, 1 mg/dose. Fifteen rats were divided randomly into three groups: control, IgAN, and IgAN fed vitamin E 100 IU/kg chow. At the end of the treatment period, rats were placed in individual metabolic cages for 24-h urine collections and then anesthetized with Inactin (100 mg/kg BW) for aspiration of peritoneal macrophages. The results (mean +/- SD) extended our previous data in male rats, confirming that the elevated proteinuria of IgAN (3.62 +/- 0.79 mg/day) was significantly reduced with vitamin E treatment (2.59 +/- 0.28 mg/day) in female rats (P < 0.002) More importantly, we indicated for the first time that oxygen free radicals production by peritoneal macrophages in IgAN was significantly reduced by vitamin E: 1.58 +/- 0.91 nmol/10(6) cells/15 min in the untreated group vs 3.28 +/- 0.54 nmol/10(6) cells/15 min in the vitamin E-treated group (P < 0.05).

[Effect of tetramethylhyrazine on proliferation of human fetal mesangial cells].

Tetramethylhyrazine (TMP) 0.6 and 1.2 mmol were added to human fetal mesangial cell (MC) cultures for 6 days, and the amounts of MC (cells/ml) were 37580 +/- 3475 and 27350 +/- 3418 respectively, significantly lower than that 71850 +/- 5108 in control (P < 0.05). The 3H-TdR incorporation by the MC with corresponding TMP were 1017 +/- 201 and 583 +/- 271, also significantly lower, than that 3575 +/- 306 in control (P < 0.01). After adding the TMP (1 mmol) to the cultures, the IL-6 bioactivity were 2118 +/- 215 that were markedly lower than those in controls (4128 +/- 351, P < 0.01). It revealed that the TMP inhibited the growth of MC and the mechanism of its inhibition might be due to that TMP could reduce the IL-6.

Pathogenesis of growth failure in renal diseases.

This article reviews our current understanding of the mechanisms of growth failure in chronic renal disease. The neuro-endocrine control of growth hormone secretion and insulin-like growth factor gene expression subject to use of corticosteroids, uremia, and metabolic acidosis are presented. It has been shown in other non-growth hormone deficient conditions such as Turner's syndrome that the use of exogenous growth hormone increases linear growth but also accelerates closure of the growth plate with no significant difference in the final height of such children. An understanding of growth factors is especially important and timely because of the tendency these days to use growth hormone to overcome the growth impairment of children with chronic renal failure.