Objective To investigate the effects of protein expressions and the urea transport activity of aldosterone on urea transporter A1 (UT-A1) and urea transporter A3 (UT-A3) in HEK293 cells and Xenopus laevis oocytes.Methods (1) Western Blot was used to investigate the protein expressions of UT-A1 and UT-A3.(2) Cell surface biotinylation was used to investigate the protein expressions of UT-A1 and UT-A3 on the cell surface of Xenopus laevis oocytes.(3) 14C-urea transport experiment was conducted to investigate the transport activity of UT-A1 and UT-A3 in Xenopus laevis oocytes.Results (1) Compared with UT-A1 or UT-A3 high expression groups,the total protein levels of UT-A 1 and UT-A3 were all significantly reduced in aldosterone treatment groups (all P < 0.01).(2) Compared with UT-A1 or UT-A3 high expression groups,the levels of protein expression on cell surface were all significantly reduced in aldosterone groups (all P < 0.01).(3) Compared with UT-A1 or UT-A3 high expression groups,14C-urea transport experiment results showed that aldosterone treatment groups had significantly reduced the urea transporter activity of UT-A1 (1 min:94.32±9.044vs 40.68±4.274,P<0.01,n=6;3 min:165.0±4.7 vs 80.3±0.6,P<0.01,n=6),and UT-A3 (1 min:204.6± 3.1 vs 176.7± 9.1,P<0.05,n=6;3 min:371.4 ± 14.9 vs 318.8 ± 12.0,P<0.05,n=6).Conclusion Aldosterone can directly down-regulate the protein expressions of UT-A1 and UT-A3 in both total protein and cell surface level,which reduces their urea transport activity.
Objective To compare the clinical efficacy of mycophenolate mofetil (MMF) and pulse cyclophosphamide (CTX) therapy combined with prednisolone in treatment of grade Ⅱ/Ⅲ Henoch-Sch(o)nlein purpura nephritis (HSPN) in children.Methods Forty-five children with grade Ⅱ/Ⅲ HSPN admitted from January 2010 to June 2015 were enrolled in the study.Among 45 patients,15 were treated with mycophenolate mofetil (MMF group) and 30 were treated with pulse cyclophosphamide (CTX group),predinisolone was simultaneously given to both groups.Clinical assessment was performed,and urine routine,24h urinary protein,serum albumin,serum creatinine,blood urea nitrogen were measured before and 1,3,6,9 and 12 months after treatment.The clinical efficacy and side effects were compared between the two groups.Results The amount of 24h urinary protein was much lower in MMF group than that of CTX group at 3,6 and 9 months after treatment(all P<0.05),the negative conversion rate of proteinuria in MMF group were higher than that in CTX group (46.7% vs 16.7%,P<0.05,86.7% vs 56.7%,P< 0.01) at 1 and 3 months after treatment.The complete remission rate of urinary RBC count (<100/μl) in MMF group was higher than that in CTX group at 3 and 6 months after treatment(60.0% vs 23.3%,73.3% vs 40.0%,both P<0.05).There was no significant difference in the total remission rate (complete remission and partial remission) between MMF and CTX(P >0.05).The complete remission rate in 6 and 9 month after treatment in MMF group was significantly higher than that in CTX group (both P< 0.05).In MMF group there was one case of gastrointestinal reaction and one case of upper respiratory tract infection.In CTX group there were 4 cases of gastrointestinal reaction,1 case of upper respiratory tract infection,and 3 cases of leukocytopenia,mild liver function damage and alopecia.Conclusion The combination therapy of MMF with steroid is more effective than CTX pulse therapy for patients with grade Ⅱ/Ⅲ HSPN in the short term.
Objective: To investigate the clinicopathological characteristics and prognosis in childhood Henoch-Sch?nlein purpura nephritis (HSPN) with or without tubulointerstitial lesions. Methods: The clinical and pathological data from 93 children with biopsy-proved HSPN were collected retrospectively in the Second Af-filiated Hospital & Yuying Children's Hospital of Wenzhou Medical University from January 2005 to December 2013. The patients were grouped according to the degree of tubulointerstitial lesions, and relationship between their clinical, glomerular parameters, prognosis and tubulointerstitial lesions was analyzed. Results: Ninety-three cases were divided into 3 groups according to the degree of tubulointerstitial lesions, group 1 with no tubuloin-terstitial lesions (16 cases, 17.2%), group 2 with mild tubulointerstitial lesions (66 cases, 71.0%), and group 3 with severe tubulointerstitial lesions (11 cases, 11.8%). The serum creatinine level (P<0.05) and the mesangial matrix score (P<0.05) was significantly higher in group 3 than that in group 1, and creatinine clearance rates of group 3 was significantly lower than that in group 1 and group 2 (P<0.05). The balloon adhesion score, fibrous crescents score and glomerulosclerosis score of group 3 were significantly higher than that in group 1 and group 2 (P<0.05). Multivariate logistic regression analysis showed that the balloon adhesion was risk factor of tubuloin-terstitial lesions. In 86 cases with follow-up, 96.5% had clinical normal or mild abnormal urine, 3.5% developed to renal dysfunction, the prognosis of group 3 was significantly worse than that in group 2 (P<0.05). Conclusion:Some HSPN patients may present with tubulointerstitial lesions in pathology at early stage of disease, which is reliable indicator for patients to develop severe glomerular lesion, and the patients with poor prognosis in future.
足细胞即肾小球脏层上皮细胞,属于终末分化细胞,位于肾小球滤过膜最外层。近十几年来随着研究技术的迅猛发展,永生化足细胞株的建立,以及足突Nephrin、Podocin等重要分子的相继发现,足细胞的研究取得了突破性进展。真核细胞结构的维持、形态变化等往往与细胞内骨架系统存在密切关系,近年来有研究表明足细胞可能是肾小球局部重要的抗原递呈细胞,因此足细胞内的细胞骨架及其相关蛋白可能也参与了足细胞的抗原递呈功能,但其具体机制远未阐明。本综述将阐述足细胞内细胞骨架及其相关蛋白I型肌球蛋白的研究进展,重点介绍其与足细胞抗原递呈的联系,为进一步研究自身免疫性肾小球肾炎靶向治疗提供方向。
Objective: To investigate the clinicopathogical characteristics and outcome of Henoch-Schon-lein purpura nephritis with endocapillary proliferation (EP-HSPN) in children.Methods: Retrospectively ana-lyzed the clinicopathology and follow-up data of children whom were biopsy-proven EP-HSPN in our hospital from January 2005 to June 2013, and the contemporary non-EP-HSPN children were chosen as control group. Further comparisons among the EP-HSPN cases were performed.Results:①In contrast to the 44 cases of non-EP-HSPN group, the 46 cases of EP-HSPN group showed younger, a shorter course of disease, joint and gastroin-testinal tract more presented involvement, nephrotic level of proteinuria, hypoalbuminemia, nephrotic syndrome type, grade III lesion, a higher rate of crescent and capillary loops necrosis, but slighter damage of renal tubular interstitial.②In 46 cases in children with EP-HSPN, compared with the 33 cases of non-DEP-HSPN, 13 cases of DEP-HSPN had heavy proteinuria, higher BUN, more showed nephrotic level of proteinuria, hypoalbuminemia and nephrotic syndrome type, less presented hematuria and proteinuria type.③For EP-HSPN children, more given steroid in combination with cyclophospamide treatment (50%), whereas for non-EP-HSPN, more given symptomatic treatment (47.7%). The follow-up results of two groups showed no statistically signiifcant differ-ences in outcome.Conclusion: EP-HSPN shows severity of clinical manifestations and glomerular pathological changes. Immunosuppressant treatment in the early stage of disease is effective for a short term outcome.