BACKGROUND: Because of the shortage of organs for transplantation, procurement of kidneys from extended criteria donors is inevitable. Frequently, donors infected with hepatitis C virus (HCV) are used. To elucidate an initial compromise of molecular pathways in HCV graft, gene expression profiles were evaluated. METHODS: Twenty-four donor allograft biopsies (n=12 HCV positive (+) and n=12 HCV negative (-)) were collected at preimplantation time and profiled using microarrays. Donors were age, race, gender, and cold and warm ischemia time matched between groups. Probe level data were read into the R programming environment using the affy Bioconductor package, and the robust multiarray average method was used to obtain probe set expression summaries. To identify probe sets exhibiting differential expression, a two sample t test was performed. Molecular and biologic functions were analyzed using Interaction Networks and Functional Analysis. RESULTS: Fifty-eight probe sets were differentially expressed between HCV (+) versus HCV (-) donors (P<0.001). The molecular functions associated with the two top scored networks from the analysis of the differentially expressed genes were connective tissue development and function and tissue morphology (score 34), cell death, cell signaling, cellular assembly, and organization (score 32). Among the differentially affected top canonical pathways, we found the role of RIG1-like receptors in antiviral innate immunity (P<0.001), natural killer cell signaling (P=0.007), interleukin-8 signaling (P=0.048), interferon signaling (P=0.0 11; INFA21, INFGR1, and MED14), ILK signaling (P=0.001), and apoptosis signaling. CONCLUSIONS: A unique gene expression pattern was identified in HCV (+) kidney grafts. Innate immune system and inflammatory pathways were the most affected.
BACKGROUND: Because of the shortage of organs for transplantation, procurement of kidneys from extended criteria donors is inevitable. Frequently, donors infected with hepatitis C virus (HCV) are used. To elucidate an initial compromise of molecular pathways in HCV graft, gene expression profiles were evaluated. METHODS: Twenty-four donor allograft biopsies (n=12 HCV positive (+) and n=12 HCV negative (-)) were collected at preimplantation time and profiled using microarrays. Donors were age, race, gender, and cold and warm ischemia time matched between groups. Probe level data were read into the R programming environment using the affy Bioconductor package, and the robust multiarray average method was used to obtain probe set expression summaries. To identify probe sets exhibiting differential expression, a two sample t test was performed. Molecular and biologic functions were analyzed using Interaction Networks and Functional Analysis. RESULTS: Fifty-eight probe sets were differentially expressed between HCV (+) versus HCV (-) donors (P<0.001). The molecular functions associated with the two top scored networks from the analysis of the differentially expressed genes were connective tissue development and function and tissue morphology (score 34), cell death, cell signaling, cellular assembly, and organization (score 32). Among the differentially affected top canonical pathways, we found the role of RIG1-like receptors in antiviral innate immunity (P<0.001), natural killer cell signaling (P=0.007), interleukin-8 signaling (P=0.048), interferon signaling (P=0.0 11; INFA21, INFGR1, and MED14), ILK signaling (P=0.001), and apoptosis signaling. CONCLUSIONS: A unique gene expression pattern was identified in HCV (+) kidney grafts. Innate immune system and inflammatory pathways were the most affected.
Authors: M A Gentil; J L Rocha; G Rodríguez-Algarra; P Pereira; R López; G Bernal; J Muñoz; M Naranjo; J Mateos Journal: Nephrol Dial Transplant Date: 1999-10 Impact factor: 5.992
Authors: A Fornasieri; M Li; S Armelloni; C P de Septis; E Schiaffino; R A Sinico; C Schmid; G D'Amico Journal: Lab Invest Date: 1993-11 Impact factor: 5.662
Authors: J Garcia-Valdecasas; C Bernal; F Garcia; S Cerezo; W O Umana; B von Albertini; P L Kimmel Journal: J Am Soc Nephrol Date: 1994-08 Impact factor: 10.121
Authors: Christine M Durand; Wanying Zhang; Diane M Brown; Sile Yu; Niraj Desai; Andrew D Redd; Serena M Bagnasco; Fizza F Naqvi; Shanti Seaman; Brianna L Doby; Darin Ostrander; Mary Grace Bowring; Yolanda Eby; Reinaldo E Fernandez; Rachel Friedman-Moraco; Nicole Turgeon; Peter Stock; Peter Chin-Hong; Shikha Mehta; Valentina Stosor; Catherine B Small; Gaurav Gupta; Sapna A Mehta; Cameron R Wolfe; Jennifer Husson; Alexander Gilbert; Matthew Cooper; Oluwafisayo Adebiyi; Avinash Agarwal; Elmi Muller; Thomas C Quinn; Jonah Odim; Shirish Huprikar; Sander Florman; Allan B Massie; Aaron A R Tobian; Dorry L Segev Journal: Am J Transplant Date: 2020-08-08 Impact factor: 9.369