Urinary exosomal transcription factors, a new class of biomarkers for renal disease.

@article{citeulike:2927944, abstract = {Urinary exosomes are excreted from all nephron segments and constitute a rich source of intracellular kidney injury biomarkers. To study whether they contain transcription factors, we collected urine from two acute kidney injury models (cisplatin or ischemia-reperfusion), two podocyte injury models (puromycin-treated rats or podocin-Vpr transgenic mice) and from patients with focal segmental glomerulosclerosis, acute kidney injury and matched controls. Exosomes were isolated by differential centrifugation and found to contain activating transcription factor 3 (ATF3) and Wilms Tumor 1 (WT-1) proteins detected by Western blot. These factors were found in the concentrated exosomal fraction, but not in whole urine. ATF3 was continuously present in urine exosomes of the rat models following acute injury at times earlier than the increase in serum creatinine. ATF3 was found in exosomes isolated from patients with acute kidney injury but not from patients with chronic kidney disease or controls. Urinary WT-1 was present in animal models before significant glomerular sclerosis and in 9/10 patients with focal segmental glomerulosclerosis but not in 8 controls. Our findings suggest that transcription factor ATF3 may provide a novel renal tubular cell biomarker for acute kidney injury while WT-1 may detect early podocyte injury. Measurement of urinary exosomal transcription factors may offer insight into cellular regulatory pathways.Kidney International advance online publication, 28 May 2008; doi:10.1038/ki.2008.206.}, address = {1Renal Diagnostics and Therapeutics Unit, National Institutes of Health, Bethesda, Maryland, USA.}, author = {Zhou, Hua and Cheruvanky, Anita and Hu, Xuzhen and Matsumoto, Takayuki and Hiramatsu, Noriyuki and Cho, Monique E E. and Berger, Alexandra and Leelahavanichkul, Asada and Doi, Kent and Chawla, Lakhmir S S. and Illei, Gabor G G. and Kopp, Jeffrey B B. and Balow, James E E. and Iii, Howard A Austin A. and Yuen, Peter St S. and Star, Robert A A. }, citeulike-article-id = {2927944}, doi = {10.1038/ki.2008.206}, issn = {1523-1755}, journal = {Kidney international}, keywords = {arf, biomarker, urine}, month = {May}, posted-at = {2008-06-26 03:56:24}, priority = {2}, title = {Urinary exosomal transcription factors, a new class of biomarkers for renal disease.}, url = {http://dx.doi.org/10.1038/ki.2008.206}, year = {2008} }

TY - JOUR ID - citeulike:2927944 L3 - citeulike-article-id:2927944 TI - Urinary exosomal transcription factors, a new class of biomarkers for renal disease. JF - Kidney international AD - 1Renal Diagnostics and Therapeutics Unit, National Institutes of Health, Bethesda, Maryland, USA. SN - 1523-1755 N2 - Urinary exosomes are excreted from all nephron segments and constitute a rich source of intracellular kidney injury biomarkers. To study whether they contain transcription factors, we collected urine from two acute kidney injury models (cisplatin or ischemia-reperfusion), two podocyte injury models (puromycin-treated rats or podocin-Vpr transgenic mice) and from patients with focal segmental glomerulosclerosis, acute kidney injury and matched controls. Exosomes were isolated by differential centrifugation and found to contain activating transcription factor 3 (ATF3) and Wilms Tumor 1 (WT-1) proteins detected by Western blot. These factors were found in the concentrated exosomal fraction, but not in whole urine. ATF3 was continuously present in urine exosomes of the rat models following acute injury at times earlier than the increase in serum creatinine. ATF3 was found in exosomes isolated from patients with acute kidney injury but not from patients with chronic kidney disease or controls. Urinary WT-1 was present in animal models before significant glomerular sclerosis and in 9/10 patients with focal segmental glomerulosclerosis but not in 8 controls. Our findings suggest that transcription factor ATF3 may provide a novel renal tubular cell biomarker for acute kidney injury while WT-1 may detect early podocyte injury. Measurement of urinary exosomal transcription factors may offer insight into cellular regulatory pathways.Kidney International advance online publication, 28 May 2008; doi:10.1038/ki.2008.206. KW - arf KW - biomarker KW - urine AU - Zhou, Hua AU - Cheruvanky, Anita AU - Hu, Xuzhen AU - Matsumoto, Takayuki AU - Hiramatsu, Noriyuki AU - Cho, Monique E AU - Berger, Alexandra AU - Leelahavanichkul, Asada AU - Doi, Kent AU - Chawla, Lakhmir S AU - Illei, Gabor G AU - Kopp, Jeffrey B AU - Balow, James E AU - Iii, Howard A Austin AU - Yuen, Peter St AU - Star, Robert A PY - 2008/05/28/ UR - http://dx.doi.org/10.1038/ki.2008.206 ER -