Fulminant metanephric apoptosis and abnormal kidney development in bcl-2-deficient mice

Sorenson, Christine M.; Rogers, Sharon A.; Korsmeyer, Stanley J.; Hammerman, Marc R.

doi:10.1152/ajprenal.1995.268.1.f73

Cited by 92 publications

(114 citation statements)

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“…As CD44 offers most resistance to apoptosis in human colon cancer cells, CD44 knockdown cells exhibit increased FoxO1, BAX, and cleaved caspase levels. These results suggest that the increased apoptosis in the CD44 knockdown group could be due to reduced clonogenic ability (19,20,(48)(49)(50). The Bcl-2 family of proteins performs antiapoptotic roles in the regulation of mitochondrial membrane permeability (33).…”

Section: Discussionmentioning

confidence: 99%

shRNA against CD44 inhibits cell proliferation, invasion and migration, and promotes apoptosis of colon carcinoma cells

Park

Huh²,

Lee³

et al. 2011

Oncol Rep

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Abstract. CD44 is a causal factor for tumor invasion, metastasis and acquisition of resistance to apoptosis. CD44 knockdown using inducible short hairpin RNA (shRNA) significantly reduces cell growth and invasion. Short hairpin RNA against CD44 and pGFP-V-RS-vector was used for knockdown of CD44 expression in SW620 colon cancer cells. Cell growth, invasion and migration assay, immunofluorescence for β-catenin expression and Western blotting for Wnt signaling molecules were analyzed. Cell cycle analysis and Western blot analysis for apoptotic molecules were evaluated. Short hairpin RNA against CD44 reduced the expression of CD44. Cell proliferation, migration and invasion were markedly inhibited and apoptosis was increased in shRNA CD44-transfected cells. Knockdown of CD44 decreased the phosphorylation of PDK1, Akt and GSK3β, and β-catenin levels. Decreased phosphorylated Akt led to an increase in phosphorylated FoxO1 and induced cell cycle arrest in the G 0 -G 1 phase and a decrease in the S phase. The levels of Bcl-2 and Bcl-xL expression were down-regulated, while the levels of BAX expression and cleaved caspase-3, -8 and -9 were increased. CD44 knockdown by way of shRNA inhibited cell proliferation and induced cell apoptosis. This can be used as a therapeutic intervention with the anti-survival/pro-apoptotic machinery in human colon cancer.

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Section: Discussionmentioning

confidence: 99%

shRNA against CD44 inhibits cell proliferation, invasion and migration, and promotes apoptosis of colon carcinoma cells

Park

Huh²,

Lee³

et al. 2011

Oncol Rep

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“…Our observations of BCL2 expression in normal human nephrogenesis accord with a recent study (49). Bcl2 null mutant mice are born with hypoplastic kidneys and metanephric growth in organ culture is restricted due to apoptosis (44,50). Thus BCL2 is required to prevent death of proliferating nephron precursors.…”

Section: Discussionmentioning

confidence: 99%

The PAX2 tanscription factor is expressed in cystic and hyperproliferative dysplastic epithelia in human kidney malformations.

Winyard

Risdon

Sams³

et al. 1996

J. Clin. Invest.

162

142

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Human dysplastic kidneys are developmental aberrations which are responsible for many of the very young children with chronic renal failure. They contain poorly differentiated metanephric cells in addition to metaplastic elements. We recently demonstrated that apoptosis was prominent in undifferentiated cells around dysplastic tubules (Winyard, P.J.D., J. Nauta, D.S. Lirenman, P. Hardman, V.R. Sams, R.A. Risdon, and A.S. Woolf. 1996. Kidney Int. 49:135-146), perhaps explaining the tendency of some of these organs to regress. In contrast, apoptosis was rare in dysplastic epithelia which are thought to be ureteric bud malformations. On occasion, these tubules form cysts which distend the abdominal cavity (the multicystic dysplastic kidney) and dysplastic kidneys may rarely become malignant. We now demonstrate that dysplastic tubules maintain a high rate of proliferation postnatally and that PAX2, a potentially oncogenic transcription factor, is expressed in these epithelia. In contrast, both cell proliferation and PAX2 are downregulated during normal maturation of human collecting ducts. We demonstrate that BCL2, a protein which prevents apoptosis in renal mesenchymal to epithelial conversion, is expressed ectopically in dysplastic kidney epithelia. We propose that dysplastic cyst formation may be understood in terms of aberrant temporal and spatial expression of master genes which are tightly regulated in the normal program of human nephrogenesis.

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“…Therefore, the present study suggests that EGF may play an important role in reduction of TUNEL positive cells in the Lp rats. This is supported by several lines of evidence as follows: superfluous apoptosis occurs in bcl-2 deficient mice and results in an increased number of apoptotic cells in the kidney [21]; EGF is one of the survival factors that protect the cells from apoptosis [19]; EGF prevents the degradation of DNA in rat renal mesenchyme [11]. Consequently, the present study reveals that low protein intake in subtotal nephrectomy in immature rats prevents renal failure and it is related to a recovery of EGF expression.…”

Section: Discussionmentioning

confidence: 57%

Effects of Low Protein Intake on the Development of the Remaining Kidney in Subtotally Nephrectomized Immature Rats: Apoptosis and Epidermal Growth Factor

Mino

Nakamura²,

Nakamuta

et al. 2007

The Journal of Veterinary Medical Science

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ABSTRACT. Effects of low protein intake on the development of the remaining kidney in subtotally (5/6) nephrectomized immature rats were examined. Three week-old weaning rats were kept on a diet containing either 12% (Lp rats) or 18% (Np rats) protein for 4 or 8 weeks after subtotal nephrectomy. Blood urea nitrogen (BUN) concentration was determined at 2, 4, 6, and 8 weeks after 5/6 nephrectomy. At 4 or 8 weeks after the operation, glomerular sclerosis and tubulointerstitial damage were assessed by a standard semiquantitative analysis and were expressed as the glomerular sclerosis index (GSI) and interstitial fibrosis score (IFS), respectively. The localization of DNA fragmented cells in the kidney was examined by the terminal deoxynucleotidyl transferase (TdT) -mediated d-UTPbiotin nick end labeling (TUNEL) method and the localization of the epidermal growth factor (EGF) by immunohistochemical methods. BUN concentration was significantly lower in the Lp rats compared with that in the Np rats. Both 4 and 8 weeks after subtotal nephrectomy, GSI and incidence of TUNEL positive cells in the distal tubules were significantly lower in the Lp rats than in the Np rats. Four weeks after the operation, IFS was significantly lower in the Lp rats than in the Np rats. Four and 8 weeks after the operation, EGF positive cells in the distal tubules were more observed in the Lp rats than in the Np rats. These findings reveal that protein restriction is effective in preventing renal tubular scarring in immature rats and that EGF is involved in the process of this prevention. KEY WORDS: EGF, immature rat, subtotal nephrectomy, TUNEL.J. Vet. Med. Sci. 69(3): 247-252, 2007 Subtotal (5/6) nephrectomy has been performed on laboratory animals to achieve a model for chronic renal failure [13,25]. The remaining kidney of 5/6 nephrectomized animals was utilized as a model for renal fibrosis [9,15,24] and a model for glomerular sclerosis [2,5]. In the remaining kidney glomerular sclerosis is observed following increased proliferative activity in glomeruli [2] and renal fibrosis is accompanied with apoptotic cells [12]. In this model, restriction of protein intake improves renal failure [6]. On the other hand, the epidermal growth factor (EGF) plays an important role in proliferative activity [16] and apoptosis [17] of the developing kidney in perinatal rats. These findings lead us to believe that both subtotal nephrectomy and restriction of protein intake greatly influence the developing kidney. Friedman and Pityer [3] have reported that low protein intake improves survival over normal protein intake in 3/4 nephrectomized immature rats. However, there is very little information available on the development of the remaining kidney in 5/6 nephrectomized immature rats. The present study was designed to clarify the effect of low protein intake on the development of the remaining kidney of subtotally nephrectomized immature rats with special reference to apoptosis and EGF. MATERIALS AND METHODS Animals and tissue processing:Three week-old m...

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Fulminant metanephric apoptosis and abnormal kidney development in bcl-2-deficient mice

Cited by 92 publications

References 0 publications

shRNA against CD44 inhibits cell proliferation, invasion and migration, and promotes apoptosis of colon carcinoma cells

shRNA against CD44 inhibits cell proliferation, invasion and migration, and promotes apoptosis of colon carcinoma cells

The PAX2 tanscription factor is expressed in cystic and hyperproliferative dysplastic epithelia in human kidney malformations.

Effects of Low Protein Intake on the Development of the Remaining Kidney in Subtotally Nephrectomized Immature Rats: Apoptosis and Epidermal Growth Factor

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