Inhibition of hyaluronan is protective against renal ischaemia-reperfusion injury
| Autor: | Nathalie Caron, Vanessa Colombaro, Virginie Voisin, Denis Nonclercq, Laetitia Giordano, Inès Jadot, Isabelle Habsch, Anne-Emilie Decleves, Bruno Flamion |
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| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Male
medicine.medical_specialty Pathology Renal function Inflammation Kidney Function Tests Pathogenesis hyaluronan Mice Fibrosis Internal medicine medicine Renal fibrosis Animals Hyaluronic Acid Transplantation Kidney business.industry fibrosis Acute kidney injury medicine.disease Mice Inbred C57BL Disease Models Animal medicine.anatomical_structure Endocrinology acute kidney injury Nephrology inflammation ischaemia-reperfusion Reperfusion Injury Indicators and Reagents medicine.symptom business Reperfusion injury Hymecromone |
| Zdroj: | Nephrology Dialysis Transplantation. 28(10):2484-2493 |
| ISSN: | 1460-2385 0931-0509 |
| Popis: | BackgroundIschaemia-reperfusion injury (IRI) to the kidney is a complex pathophysiological process that leads to acute renal failure and chronic dysfunction in renal allografts. It was previously demonstrated that during IRI, hyaluronan (HA) accumulates in the cortical and external medullary interstitium along with an increased expression of its main receptor, CD44, on inflammatory and tubular cells. The HA-CD44 pair may be involved in persistent post-ischaemic inflammation. Thus, we sought to determine the role of HA in the pathophysiology of ischaemia-reperfusion (IR) by preventing its accumulation in post-ischaemic kidney.MethodsC57BL/6 mice received a diet containing 4-methylumbelliferone (4-MU), a potent HA synthesis inhibitor. At the end of the treatment, unilateral renal IR was induced and mice were euthanized 48 h or 30 days post-IR.Results4-MU treatment for 14 weeks reduced the plasma HA level and intra-renal HA content at 48 h post-IR, as well as CD44 expression, creatininemia and histopathological lesions. Moreover, inflammation was significantly attenuated and proliferation was reduced in animals treated with 4-MU. In addition, 4-MU-treated mice had a significantly reduced expression of α-SMA and collagen types I and III, i.e. less renal fibrosis, 30 days after IR compared with untreated mice.ConclusionOur results demonstrate that HA plays a significant role in the pathogenesis of IRI, perhaps in part through reduced expression of CD44. The suppression of HA accumulation during IR may protect renal function against ischaemic insults. © 2013 The Author. All rights reserved. |
| Databáze: | OpenAIRE |
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