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Publication : Cyclophilin A Promotes Inflammation in Acute Kidney Injury but Not in Renal Fibrosis.

First Author  Leong KG Year  2020
Journal  Int J Mol Sci Volume  21
Issue  10 PubMed ID  32455976
Mgi Jnum  J:302499 Mgi Id  MGI:6508176
Doi  10.3390/ijms21103667 Citation  Leong KG, et al. (2020) Cyclophilin A Promotes Inflammation in Acute Kidney Injury but Not in Renal Fibrosis. Int J Mol Sci 21(10):3667
abstractText  Cyclophilin A (CypA) is a highly abundant protein in the cytoplasm of most mammalian cells. Beyond its homeostatic role in protein folding, CypA is a Damage-Associated Molecular Pattern which can promote inflammation during tissue injury. However, the role of CypA in kidney disease is largely unknown. This study investigates the contribution of CypA in two different types of kidney injury: acute tubular necrosis and progressive interstitial fibrosis. CypA (Ppia) gene deficient and wild type (WT) littermate controls underwent bilateral renal ischaemia/reperfusion injury (IRI) and were killed 24h later or underwent left unilateral ureteric obstruction (UUO) and were killed 7 days later. In the IRI model, CypA(-/-) mice showed substantial protection against the loss of renal function and from tubular cell damage and death. This was attributed to a significant reduction in neutrophil and macrophage infiltration since CypA(-/-) tubular cells were not protected from oxidant-induced cell death in vitro. In the UUO model, CypA(-/-) mice were not protected from leukocyte infiltration or renal interstitial fibrosis. In conclusion, CypA promotes inflammation and acute kidney injury in renal IRI, but does not contribute to inflammation or interstitial fibrosis in a model of progressive kidney fibrosis.
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