PMID- 16495380 OWN - NLM STAT- MEDLINE DCOM- 20060928 LR - 20161019 IS - 1046-6673 (Print) IS - 1046-6673 (Linking) VI - 17 IP - 4 DP - 2006 Apr TI - Role of ubiquitin-like protein FAT10 in epithelial apoptosis in renal disease. PG - 996-1004 AB - Dysregulated apoptosis of renal tubular epithelial cells (RTEC) is an important component of the pathogenesis of several renal diseases, including HIV-associated nephropathy (HIVAN), the most common cause of chronic kidney failure in HIV-infected patients. In HIVAN, RTEC become infected by HIV-1 in a focal distribution, and HIV-1 infection has been shown to induce apoptosis in vitro. In microarray studies that used a novel renal tubular epithelial cell line from a patient with HIVAN, it was found that the ubiquitin-like protein FAT10 is one of the most upregulated genes in HIV-infected cells. Previously, FAT10 was shown to induce apoptosis in murine fibroblasts. The expression of FAT10 in HIVAN and the ability of FAT10 to induce apoptosis in human RTEC therefore were studied. This study revealed that FAT10 expression is induced after infection of RTEC by HIV-1 and that expression of FAT10 induces apoptosis in RTEC in vitro. Moreover, it was found that inhibition of endogenous FAT10 expression abrogated HIV-induced apoptosis of RTEC. Immunohistochemical studies demonstrated increased FAT10 expression in a murine model of HIVAN, in HIVAN biopsy samples, and in autosomal dominant polycystic kidney disease, another renal disease that is characterized by cystic tubular enlargement and epithelial apoptosis. These results suggest a novel role for FAT10 in epithelial apoptosis, which is an important component of the pathogenesis of many renal diseases. FAU - Ross, Michael J AU - Ross MJ AD - Mount Sinai School of Medicine, Division of Nephrology, Box 1243, One Gustave L. Levy Place, New York, NY 10029, USA. michael.ross@mssm.edu FAU - Wosnitzer, Matthew S AU - Wosnitzer MS FAU - Ross, Michael D AU - Ross MD FAU - Granelli, Benedetta AU - Granelli B FAU - Gusella, G Luca AU - Gusella GL FAU - Husain, Mohammad AU - Husain M FAU - Kaufman, Lewis AU - Kaufman L FAU - Vasievich, Matthew AU - Vasievich M FAU - D'Agati, Vivette D AU - D'Agati VD FAU - Wilson, Patricia D AU - Wilson PD FAU - Klotman, Mary E AU - Klotman ME FAU - Klotman, Paul E AU - Klotman PE LA - eng GR - K08 DK062672/DK/NIDDK NIH HHS/United States GR - K08 DK 62672/DK/NIDDK NIH HHS/United States GR - P01 DK 056492/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20060222 PL - United States TA - J Am Soc Nephrol JT - Journal of the American Society of Nephrology : JASN JID - 9013836 RN - 0 (DNA, Complementary) RN - 0 (FAT10 protein, mouse) RN - 0 (RNA, Messenger) RN - 0 (UBD protein, human) RN - 0 (Ubiquitins) SB - IM MH - AIDS-Associated Nephropathy/genetics/metabolism/pathology MH - Animals MH - Apoptosis/physiology MH - Base Sequence MH - Cell Line MH - DNA, Complementary/genetics MH - Gene Expression MH - HIV-1 MH - Humans MH - Kidney Diseases/genetics/*metabolism/*pathology MH - Kidney Tubules, Proximal/metabolism/pathology MH - Mice MH - Mice, Transgenic MH - Molecular Sequence Data MH - Polycystic Kidney, Autosomal Dominant/genetics/metabolism/pathology MH - RNA, Messenger/genetics/metabolism MH - Ubiquitins/genetics/*metabolism EDAT- 2006/02/24 09:00 MHDA- 2006/09/29 09:00 CRDT- 2006/02/24 09:00 PHST- 2006/02/24 09:00 [pubmed] PHST- 2006/09/29 09:00 [medline] PHST- 2006/02/24 09:00 [entrez] AID - ASN.2005070692 [pii] AID - 10.1681/ASN.2005070692 [doi] PST - ppublish SO - J Am Soc Nephrol. 2006 Apr;17(4):996-1004. doi: 10.1681/ASN.2005070692. Epub 2006 Feb 22.