Dysregulated growth factor gene expression is associated with tubulointerstitial apoptosis and renal dysfunction

Chronic renal disease is characterized by declining renal function, loss of intrinsic renal cells, and their replacement with fibrotic tissue. This study investigates apoptosis and its regulation in the context of chronic renal disease. RNA was extracted from renal biopsies from patients with variou...

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Veröffentlicht in:Kidney international 2007-05, Vol.71 (10), p.1044-1053
Hauptverfasser: Teteris, S.A., Menahem, S.A., Perry, G., Maguire, J.A., Dowling, J.P., Langham, R.G., Thomson, N.M., Stein, A.N.
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container_issue 10
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container_title Kidney international
container_volume 71
creator Teteris, S.A.
Menahem, S.A.
Perry, G.
Maguire, J.A.
Dowling, J.P.
Langham, R.G.
Thomson, N.M.
Stein, A.N.
description Chronic renal disease is characterized by declining renal function, loss of intrinsic renal cells, and their replacement with fibrotic tissue. This study investigates apoptosis and its regulation in the context of chronic renal disease. RNA was extracted from renal biopsies from patients with various forms of chronic renal disease. Expression of genes of the Bcl-2 family, death receptor pathway, and growth factors were measured by reverse-transcription real-time polymerase chain reaction. Apoptosis was detected by the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end-labeling technique. Tubulointerstitial apoptosis was positively associated with tubulointerstitial injury and renal dysfunction and increased 2.3-fold per unit (U) increase in transforming growth factor β1 (TGFβ1) mRNA (P
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This study investigates apoptosis and its regulation in the context of chronic renal disease. RNA was extracted from renal biopsies from patients with various forms of chronic renal disease. Expression of genes of the Bcl-2 family, death receptor pathway, and growth factors were measured by reverse-transcription real-time polymerase chain reaction. Apoptosis was detected by the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end-labeling technique. Tubulointerstitial apoptosis was positively associated with tubulointerstitial injury and renal dysfunction and increased 2.3-fold per unit (U) increase in transforming growth factor β1 (TGFβ1) mRNA (P<0.05). Conversely, a 1U increase in epidermal growth factor (EGF) mRNA was associated with a 47% decrease in tubulointerstitial apoptosis (P<0.05). Tubulointerstitial injury was correlated with increased TGFβ1 and tumour necrosis factor α (TNFα) mRNA (P<0.005) and decreased EGF mRNA (P<0.05). Additionally, for a 10U decrease in the glomerular filtration rate there was an estimated increase of 5 and 10% in TGFβ1 and TNFα mRNA, respectively (P<0.05), whereas EGF mRNA decreased by an estimated 15% (P<0.005). Therefore dysregulation of cytokine/growth factor expression plays a central role in the progression of chronic renal disease through contribution to renal cell loss, tubulointerstitial injury, and renal dysfunction.]]></description><identifier>ISSN: 0085-2538</identifier><identifier>EISSN: 1523-1755</identifier><identifier>DOI: 10.1038/sj.ki.5002176</identifier><identifier>PMID: 17361117</identifier><identifier>CODEN: KDYIA5</identifier><language>eng</language><publisher>New York, NY: Elsevier Inc</publisher><subject>Adult ; Aged ; Aged, 80 and over ; apoptosis ; Apoptosis - genetics ; Biological and medical sciences ; Biomarkers - blood ; Biopsy ; Chronic Disease ; chronic renal disease ; epidermal growth factor ; Epidermal Growth Factor - genetics ; Female ; Gene Expression ; Gene Expression Regulation ; Glomerular Filtration Rate ; Humans ; Intercellular Signaling Peptides and Proteins - genetics ; Kidney - pathology ; Kidney - physiopathology ; Kidney Diseases - complications ; Kidney Diseases - genetics ; Kidney Diseases - pathology ; Kidney Diseases - physiopathology ; Kidney Tubules - physiopathology ; Kidneys ; Male ; Medical sciences ; Middle Aged ; Nephrology. Urinary tract diseases ; Nephropathies. Renovascular diseases. Renal failure ; Proteinuria - etiology ; Renal failure ; RNA, Messenger - metabolism ; TGF beta ; TNF alpha ; Transforming Growth Factor beta1 - genetics ; Treatment Outcome ; Tumor Necrosis Factor-alpha - genetics ; Urinary system involvement in other diseases. 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This study investigates apoptosis and its regulation in the context of chronic renal disease. RNA was extracted from renal biopsies from patients with various forms of chronic renal disease. Expression of genes of the Bcl-2 family, death receptor pathway, and growth factors were measured by reverse-transcription real-time polymerase chain reaction. Apoptosis was detected by the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end-labeling technique. Tubulointerstitial apoptosis was positively associated with tubulointerstitial injury and renal dysfunction and increased 2.3-fold per unit (U) increase in transforming growth factor β1 (TGFβ1) mRNA (P<0.05). Conversely, a 1U increase in epidermal growth factor (EGF) mRNA was associated with a 47% decrease in tubulointerstitial apoptosis (P<0.05). Tubulointerstitial injury was correlated with increased TGFβ1 and tumour necrosis factor α (TNFα) mRNA (P<0.005) and decreased EGF mRNA (P<0.05). Additionally, for a 10U decrease in the glomerular filtration rate there was an estimated increase of 5 and 10% in TGFβ1 and TNFα mRNA, respectively (P<0.05), whereas EGF mRNA decreased by an estimated 15% (P<0.005). Therefore dysregulation of cytokine/growth factor expression plays a central role in the progression of chronic renal disease through contribution to renal cell loss, tubulointerstitial injury, and renal dysfunction.]]></description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>apoptosis</subject><subject>Apoptosis - genetics</subject><subject>Biological and medical sciences</subject><subject>Biomarkers - blood</subject><subject>Biopsy</subject><subject>Chronic Disease</subject><subject>chronic renal disease</subject><subject>epidermal growth factor</subject><subject>Epidermal Growth Factor - genetics</subject><subject>Female</subject><subject>Gene Expression</subject><subject>Gene Expression Regulation</subject><subject>Glomerular Filtration Rate</subject><subject>Humans</subject><subject>Intercellular Signaling Peptides and Proteins - genetics</subject><subject>Kidney - pathology</subject><subject>Kidney - physiopathology</subject><subject>Kidney Diseases - complications</subject><subject>Kidney Diseases - genetics</subject><subject>Kidney Diseases - pathology</subject><subject>Kidney Diseases - physiopathology</subject><subject>Kidney Tubules - physiopathology</subject><subject>Kidneys</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Nephrology. Urinary tract diseases</subject><subject>Nephropathies. Renovascular diseases. Renal failure</subject><subject>Proteinuria - etiology</subject><subject>Renal failure</subject><subject>RNA, Messenger - metabolism</subject><subject>TGF beta</subject><subject>TNF alpha</subject><subject>Transforming Growth Factor beta1 - genetics</subject><subject>Treatment Outcome</subject><subject>Tumor Necrosis Factor-alpha - genetics</subject><subject>Urinary system involvement in other diseases. 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This study investigates apoptosis and its regulation in the context of chronic renal disease. RNA was extracted from renal biopsies from patients with various forms of chronic renal disease. Expression of genes of the Bcl-2 family, death receptor pathway, and growth factors were measured by reverse-transcription real-time polymerase chain reaction. Apoptosis was detected by the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end-labeling technique. Tubulointerstitial apoptosis was positively associated with tubulointerstitial injury and renal dysfunction and increased 2.3-fold per unit (U) increase in transforming growth factor β1 (TGFβ1) mRNA (P<0.05). Conversely, a 1U increase in epidermal growth factor (EGF) mRNA was associated with a 47% decrease in tubulointerstitial apoptosis (P<0.05). Tubulointerstitial injury was correlated with increased TGFβ1 and tumour necrosis factor α (TNFα) mRNA (P<0.005) and decreased EGF mRNA (P<0.05). Additionally, for a 10U decrease in the glomerular filtration rate there was an estimated increase of 5 and 10% in TGFβ1 and TNFα mRNA, respectively (P<0.05), whereas EGF mRNA decreased by an estimated 15% (P<0.005). Therefore dysregulation of cytokine/growth factor expression plays a central role in the progression of chronic renal disease through contribution to renal cell loss, tubulointerstitial injury, and renal dysfunction.]]></abstract><cop>New York, NY</cop><pub>Elsevier Inc</pub><pmid>17361117</pmid><doi>10.1038/sj.ki.5002176</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record>
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subjects Adult
Aged
Aged, 80 and over
apoptosis
Apoptosis - genetics
Biological and medical sciences
Biomarkers - blood
Biopsy
Chronic Disease
chronic renal disease
epidermal growth factor
Epidermal Growth Factor - genetics
Female
Gene Expression
Gene Expression Regulation
Glomerular Filtration Rate
Humans
Intercellular Signaling Peptides and Proteins - genetics
Kidney - pathology
Kidney - physiopathology
Kidney Diseases - complications
Kidney Diseases - genetics
Kidney Diseases - pathology
Kidney Diseases - physiopathology
Kidney Tubules - physiopathology
Kidneys
Male
Medical sciences
Middle Aged
Nephrology. Urinary tract diseases
Nephropathies. Renovascular diseases. Renal failure
Proteinuria - etiology
Renal failure
RNA, Messenger - metabolism
TGF beta
TNF alpha
Transforming Growth Factor beta1 - genetics
Treatment Outcome
Tumor Necrosis Factor-alpha - genetics
Urinary system involvement in other diseases. Miscellaneous
title Dysregulated growth factor gene expression is associated with tubulointerstitial apoptosis and renal dysfunction
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