Fibrinogen β–derived Bβ15-42 peptide protects against kidney ischemia/ reperfusion injury
| Autor: | Tae-Min Kim, Dana Hoffmann, Aparna Krishnamoorthy, Amrendra Kumar Ajay, Victoria Ramírez, Gabriela Campanholle, Norma A. Bobadilla, Vishal S. Vaidya, Sushrut S. Waikar |
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| Rok vydání: | 2011 |
| Předmět: |
Male
Pathology medicine.medical_specialty Urinary system Molecular Sequence Data Immunology Ischemia Apoptosis Biology Kidney Biochemistry Thrombosis and Hemostasis Fibrin Fibrinogen Degradation Products Mice Reperfusion therapy medicine Animals Humans Amino Acid Sequence RNA Messenger Rats Wistar Aged Renal ischemia urogenital system Acute kidney injury Fibrinogen Cell Biology Hematology Acute Kidney Injury Middle Aged medicine.disease Peptide Fragments Rats Up-Regulation Mice Inbred C57BL medicine.anatomical_structure Reperfusion Injury Female Reperfusion injury Kidney disease |
| Zdroj: | Blood. 118:1934-1942 |
| ISSN: | 1528-0020 0006-4971 |
| DOI: | 10.1182/blood-2011-02-338061 |
| Popis: | 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 Bβ15-42 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. |
| Databáze: | OpenAIRE |
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