title: Fibrinogen β-derived Bβ(15-42) peptide protects against kidney ischemia/reperfusion injury.
abstract: Ischemia/reperfusion (I/R) injury in the kidney is a major cause of acute kidney injury (AKI) in humans and is associated with significantly high mortality. To identify genes that modulate kidney injury and repair, we conducted genome-wide expression analysis in the rat kidneys after I/R and found that the mRNA levels of fibrinogen (Fg)α, Fgβ, and Fgγ chains significantly increase in the kidney and remain elevated throughout the regeneration process. Cellular characterization of Fgα and Fgγ chain immunoreactive proteins shows a predominant expression in renal tubular cells and the localization of immunoreactive Fgβ chain protein is primarily in the renal interstitium in healthy and regenerating kidney. We also show that urinary excretion of Fg is massively increased after kidney damage and is capable of distinguishing human patients with acute or chronic kidney injury (n = 25) from healthy volunteers (n = 25) with high sensitivity and specificity (area under the receiver operating characteristic of 0.98). Furthermore, we demonstrate that Fgβ-derived Bβ(15-42) peptide administration protects mice from I/R-induced kidney injury by aiding in epithelial cell proliferation and tissue repair. Given that kidney regeneration is a major determinant of outcome for patients with kidney damage, these results provide new opportunities for the use of Fg in diagnosis, prevention, and therapeutic interventions in kidney disease.
authors.affiliation: Renal Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
authors.forename: Aparna
authors.initials: A
authors.lastname: Krishnamoorthy
authors.forename: Amrendra Kumar
authors.initials: AK
authors.lastname: Ajay
authors.forename: Dana
authors.initials: D
authors.lastname: Hoffmann
authors.forename: Tae-Min
authors.initials: TM
authors.lastname: Kim
authors.forename: Victoria
authors.initials: V
authors.lastname: Ramirez
authors.forename: Gabriela
authors.initials: G
authors.lastname: Campanholle
authors.forename: Norma A
authors.initials: NA
authors.lastname: Bobadilla
authors.forename: Sushrut S
authors.initials: SS
authors.lastname: Waikar
authors.forename: Vishal S
authors.initials: VS
authors.lastname: Vaidya
mesh_terms: D058186:Acute Kidney Injury / Q000188:drug therapy* / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D000368:Aged; D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000627:therapeutic use*; D005340:Fibrinogen / Q000235:genetics / Q000276:immunology / Q000652:urine; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000150:complications*; D015854:Up-Regulation
chemical_list: D005338:Fibrin Fibrinogen Degradation Products; D010446:Peptide Fragments; D012333:RNA, Messenger; C033786:fibrinogen Bbeta (15-42); D005340:Fibrinogen