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Effect of Aldosterone on Expression of Thrombospondin-1 and Proliferation in Human Proximal Tubular Epithelial Cells

Author: LiuZhiZuo
Tutor: GuoZhiJun
School: Hebei Medical University
Course: Internal Medicine
Keywords: aldosterone renal proximal tubular epithelial cells proliferation thrombospondin 1
CLC: R692
Type: Master's thesis
Year: 2008
Downloads: 46
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Objective: Renal tubulointerstitial fibrosis is viewed as the final common pathway to renal failure, regardless of the initiating injury. Although the mechanisms of the interstitial are not exactly known, it has been shown in a number of clinical as well as experimental studies that tubulointerstitial injury is a consistent predictor of functional impairment rather than glomerular damage. The direct causes of this process are the over-production and blunted degradation of extracellular matrix (ECM). Studies have shown that thrombospondin-1 (TSP-1) acts as an activating factor of TGF-β1,which expression is increased in a variety of human and experimental diseases characterized by fibrosis, especially in the kidney fibrosis diseases, suggesting its crucial roles in tubulointerstitial fibrosis .Various studies have shown that the renin-angiotensin- aldosterone system (RAAS) plays an important role in the development and progression of renal diseases. Over the past decades, although more evidence demonstrated conclusively that angiotensin II (Ang II) mediates renal function and structural damage in various kidney diseases. Recent experimental and clinical studies also implicate aldosterone (ALD) as an important pathogenesis factor in progressive renal disease through both hemodynamic effects and direct cellular actions, which has the function of non-dependent Ang II especially in stimulating organ fibrosis, but the way is unknown. Many animal model of renal failure and patients of chronic renal failure have found high expression of ALD, ALD plays the important role of continuous damage in remnant kidney. ALD fosters progressive renal injury; the underlying mechanisms for the pathological actions are not understood. Recent studies have shown that ALD not only regulated water and sodium balance, but also promote collagen deposition、fibrosis , such as kidney、heart and ventricles. ALD, which synthesized in kidney, can also promote collagen deposition, up-regulate fibrosis cytokine, effect hypertension by the regulate of vessel intensity, effect function of cells by the regulate of synthesize and function of Na+-K+-ATPase. ALD can stimulate the thicken of tubular membrane, shrink of tubular epithelial cells, up-regulate TGF-β, induce tubular epithelial cells transdifferentiation to MFB, increase ECM deposition such as collagenⅠ,Ⅳand fibronetion (FN), thus to accelerate tubulointerstitial fibrosis.Some studies have shown that there is no expression of TSP-1 in human proximal tubular epithelial cells, if stimulating human proximal tubular epithelial cells, the expression of TSP-1 will increase. However,what’s the effect of ALD on the expression of TSP-1 in human proximal tubular epithelial cells? Can it enhance the expression of TSP-1, thus promote the progression of tubulointerstitial injury? The purpose of our study is to determine the possible effect of ALD on expression of TSP-1 and proliferation in cultured human proximal tubular epithelial cells in vitro, thereby to explore the role of aldosterone in tubulointerstitial fibrosis and its mechanism.Methods: 1 Culture of the human proximal tubular cells (HKCs): HKCs was purchased from Cell Culture Center of Peking Union Medical College. The cells were maintained at 37℃in an atmosphere of 5% CO2 in DMEM/F12, containing 10% FBS, 100 U/L penicillin, and 100 mg/L streptomycin. The experiment divided into two groups: control group and ALD group, to observe the effect of different concentration (10-9, 10-8, 10-7, 10-6mol/L) ALD and time (24 h, 48 h and 72 h by 10-6mol/L ALD on HKCs) on expression of TSP-1 mRNA proliferation in cultured human proximal tubular epithelial cells.2 The response of TSP-1 mRNA expression to ALD stimulation was observed by semi-quantitative RT-PCR;3 The proliferate effects of aldosterone were evaluated by methylene blue (MTT) assay.4 The data were shown by±s; the statistics analysis was described by spss10.0 software.Results: 1 The results of RT-PCR indicate that the human proximal tubular epithelial cells don’t express TSP-1 in the nomol condition; ALD can induce the expression of TSP-1 (compa red with control group, P <0.01).TSP-1 mRNA was increased significantly by ALD in a dose-dependent and time-dependent manner;2 ALD promoted the proliferation of HKCs in a dose-dependent and time-dependent manner by MTT assay (compared with control group, P <0.01). Conclusion: 1 The human proximal tubular epithelial cells don’t express TSP-1 in the nomol condition 2 ALD may induce TSP-1 mRNA expression in a dose-dependent and time-dependent manner;3 ALD can promote the proliferation of HKCS in a dose-dependent and time-dependent manner.4 ALD perhaps stimulate the proliferation、hypertrophy、transdifferention and apoptosis of proximal tubular epithelial cells, causes the over-production of ECM, promote the progression of renal tubulointerstitial fibrosis by inducing the secrete of TSP-1. Our studies suggest a possible role in the progression of renal failure by inhibit the affect of ALD, afford new clinical therapy for chronic renal failure.

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CLC: > Medicine, health > Surgery > Urology ( urinary and reproductive system diseases) > Kidney disease
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