title: Selenium-binding protein-1 in smooth muscle cells is downregulated in a rhesus monkey model of chronic allograft nephropathy.
abstract: Treating patients with kidney failure by organ transplantation has been extraordinarily successful. Although, current immunosuppressants have improved short-term allograft survival, most transplants are eventually lost due to chronic allograft nephropathy (CAN). The molecular mechanisms underlying CAN are poorly understood. Smooth muscle cells (SMC) play a major role in the pathogenesis of CAN by contributing to the thickening of the intima and narrowing of the lumen of blood vessels. We show that selenium-binding protein-1 (SBP-1), a protein implicated in protein trafficking and secretion, is localized primarily to SMC in vivo. SBP-1 was heavily tyrosine-phosphorylated in vivo. Remarkably, SBP-1 was absent or strongly downregulated in vascular SMC in monkey kidney allografts with CAN. In contrast, the SMC alpha-actin was strongly expressed in the vascular SMC of the same allografts, indicating that the decrease in SBP-1 was not due to a global decrease in SMC proteins. Out of four growth factors implicated in the pathogenesis of CAN, only TGF-beta blocked the expression of SBP-1; thus, TGF-beta could regulate the expression of SBP-1 in CAN. These results show that SBP-1 localizes primarily to SMC in vivo and implicate this phosphoprotein in the effects of TGF-beta on SMC and in the process of CAN.
authors.affiliation: Department of Pathology, University of Wisconsin-Madison, WI, USA.
authors.forename: Jose R
authors.initials: JR
authors.lastname: Torrealba
authors.forename: Matthew
authors.initials: M
authors.lastname: Colburn
authors.forename: Susan
authors.initials: S
authors.lastname: Golner
authors.forename: Zhen
authors.initials: Z
authors.lastname: Chang
authors.forename: Tara
authors.initials: T
authors.lastname: Scheunemann
authors.forename: John H
authors.initials: JH
authors.lastname: Fechner
authors.forename: Drew
authors.initials: D
authors.lastname: Roenneburg
authors.forename: Huaizhong
authors.initials: H
authors.lastname: Hu
authors.forename: Tausif
authors.initials: T
authors.lastname: Alam
authors.forename: Hyoung T
authors.initials: HT
authors.lastname: Kim
authors.forename: Turan
authors.initials: T
authors.lastname: Kanmaz
authors.forename: Terry
authors.initials: T
authors.lastname: Oberley
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: Knechtle
authors.forename: Majed M
authors.initials: MM
authors.lastname: Hamawy
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002352:Carrier Proteins / Q000096:biosynthesis*; D002460:Cell Line; D003331:Coronary Vessels / Q000378:metabolism; D003902:Detergents / Q000494:pharmacology; D004195:Disease Models, Animal; D015536:Down-Regulation; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007668:Kidney / Q000378:metabolism; D007674:Kidney Diseases / Q000378:metabolism; D008253:Macaca mulatta; D013058:Mass Spectrometry; D009130:Muscle, Smooth / Q000166:cytology*; D009393:Nephritis / Q000378:metabolism*; D010750:Phosphoproteins / Q000737:chemistry; D010766:Phosphorylation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051137:Selenium-Binding Proteins; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism; D014599:Uterus / Q000378:metabolism
chemical_list: D000199:Actins; D002352:Carrier Proteins; D003902:Detergents; D007166:Immunosuppressive Agents; D010750:Phosphoproteins; C495175:SELENBP1 protein, human; D051137:Selenium-Binding Proteins; D016212:Transforming Growth Factor beta; D014443:Tyrosine