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Parathyroid hormone-related protein (PTHrP) and its receptor type 1 (PTH1 R) are extensively expressed in the kidney,where they are able to modulate renal function.Animal and human studies have shown that PTHrP acts as an important mediator of diabetic renal cell hypertrophy by a meehanism which involves the modulation of cell cycle regulatory proteins and TGF-β1.Furthermore,angiotensin Ⅱ (Ang Ⅱ) appears to be responsible for PTHrP upregulation in these conditions.These findings provide novel insights into the well-known protective effects of Ang Ⅱ antagonists in renal diseases,paving the wav for new therapeutic approaches.
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Acute kidney injury(AKI) has emerged as a major public health problem that leads to decreased survival.In AKI,cell hyperplasia,hypertrophy and apoptosis are related to the cell cycle control.Two supervisory restriction points,G1/S and G2/M checkpoints,are responsible for cell-cycle control.Furthermore,cell cycle regulatory proteins are also involved in the regulation of the cell cycle in AKI.This review focuses on the cell cycle regulation mechanism of AKI.
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Objective To investigate the radiosensitization of artesunate on nude mouse transplanted with HeLa cells,and to explore its possible mechanisms.Methods HeLa cells were inoculated into the nude mice to establish tumor model.Mice were randomly divided into 4 groups as blank control,artesunate group,radiation group and artesunate + radiation group when average volume of tumor were about 5 mm × 5 mm× 5 mm.During the term of treatment,the volume of tumors were measured every 2days.After 14 days treatment,the mice were killed and tumor tissues were harvested for flow cytometry to detect the alteration of cell cycle.Meanwhile,the pathological change of the tumor tissue was observed with HE staining method,and the change of expression of cycle regulatory protein Cyclin B1,Cdc2 and Wee1 were detected by Western blot.Results The growth of tumor was significantly inhibited by artesunate combined with radiation and its inhibition rate was 72.34％.Flow cytometry results showed that the percent of cells in G1 phase increased and G2 phase decreased in the artesunate + radiation group compared with those in irradiation group ( t =4.41,4.12,P ＜ 0.05 ).The expression level of Cyclin B1 was obviously increased while that of Wee1 decreased in the artesunate + radiation compared with irradiation group.There was no difference in the expression of Cdc2 among the four groups.Conclusions Artesunate can dramatically increase the radiosensitivity of transplanted tumor of HeLa cells.The possible mechanism might be related to the decreasing G2 phase by regulating the expression of Cyclin B1 and Wee1.
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Aim To investigate the effect of taurine(Tau)on the cardiac fibroblast(CFb)cell cycle and its regulatory protein expression,and to explore the underlying mechanism of Tau-inhibiting the proliferation of CFb.Methods The proliferation of cultured neonatal rat CFb was induced by Angiotensin Ⅱ and detected by the thiazole blue(MTT)colorimetric assay.Hydroxyproline measurement was carried out to detect the collagen quantification.The expression of cell cycle regulatory protein cyclin D and p27 were determined by the combination of immunocytochemical staining and image analysis software.Cell cycle and p27 were assessed via flow cytometry.Results CFb proliferation and hydroxyproline content in culture medium were markedly inhibited when CFb were treated with taurine at concentrations of 40,80 and 160 mmol?L-1 for 24 hours(P
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catechin plus dexamethasone-treated group. Compared with nephrotic group, the renal pathologic score were significantly different among the nephrotic group and the catechin-treated group (6 80?0 84,P
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Objective To examine the expression of cell cycle regulatory protiens in renal tubulointerstitial cells of human glomerulonephritis. Methods Immunohisochemieal studies were performed on 19 specimen from renal biopsy to detect cyclin Dl, cyclin A, p21 and proliferating nuclear antigen (PCNA) . Results Cyclin Dl, cyclin A and p21 were positive in some of tubulointerstitial cells, and showed significant correlations with positive PCNA cells. The numbers of tubular positive cells in both groupsofⅠand Ⅱ degree of histopathological change were more than those of other groups. The numbers of interstitialpositive cells showed significant correlations with the degree of tubulointerstitial histopathological change and the value of urine NAG. Conclusion Cell cycle regulatory proteins regulate the proliferation of tubular and interstitial cells, and correlate with the interstitial fibrosis.
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Objective Our study aimed at the role of p27 on the hypertrophy of mesangial cell (MC) cultured in high glucose. Methods The p27 protein of MC lysate was detected with western blotting analysis. The degree of cultured MC hypertrophy was estimated through [3H]-thymidine incorporation and [3H]-leucine incorporation. The effect of reducing p27 expression on cell hypertrophy was analysed with p27 antisense oligodeoxynucleotide (ODN) phosphorothioate. Results in MC cultured in high glucose (450mg/dl) serum-free DMEM compared with MC cultured in normal glucose (100mg/dl) serum-free DMEM, p27 increased, [3H]-leucine incorporation increased and[3H]-thymidine incorporation decreased;p27 antisense ODN transfection reduced [3H]leucine incorporation, increased [3H] thymidine incorporation of MC cultured in high glucose senumfree DMEM. Increasing medium osmolarity with D-mannitol failed to induce p27 expression of MC. Conclusion p27 protein increased in MC cultured in high glucose. High level of p27 played an important role in MC hypertrophy induced by high glucose. Because the cell cycle is controlled by the interaction between the positive cell cycle regulatory proteins(CCRP) and negative CCRP, further research is needed to study the expression of the positive and negative CCRP in MC in order to better understand the role of CCRP in MC hypertrophy.
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Objective: To investigate the role of cyclin kinase inhibitor P27 on the proliferation of mesangial cell(MC) in Thy1 glomerulonephritis(GN) rats. Methods: The Thy1 model of experimental mesangial proliferative glomerulonephritis was induced by intravenous injection of rabbit anti-thymocyte plasma. The P27 protein of glomerular lysate was detected with Western blotting analysis. The P27 mRNA was determined with RT-PCR. The extracellular matrix (ECM) protein (fibronectin and type Ⅳ collagen) of glomerular lysate was examined with ELISA. Results: Glomerular P27 protein of Thy1 model rat decreased compared with that of normal rat. The level of P27 was associated with the degree of MC proliferation:P27 began to decrease on day 1 in Thy1 model, then reached the lowest on day 3 when MC proliferation was maximal, then returned to 60% of the baseline level on day 5 when MC proliferation began to resolute. Glomeruar P27 mRNA remained constant in Thy1 GN(3 d) rats. Glomerular fibronectin(Fn) and type Ⅳ collagen increased in Thy1 model: They reached the highest on day 3(P