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

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 unknow...

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Main Authors: Khai Gene Leong, Elyce Ozols, John Kanellis, David J. Nikolic-Paterson, Frank Y. Ma
Format: Article
Language:English
Published: MDPI AG 2020-05-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/21/10/3667
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author Khai Gene Leong
Elyce Ozols
John Kanellis
David J. Nikolic-Paterson
Frank Y. Ma
author_facet Khai Gene Leong
Elyce Ozols
John Kanellis
David J. Nikolic-Paterson
Frank Y. Ma
author_sort Khai Gene Leong
collection DOAJ
description 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. <i>CypA (Ppia)</i> gene deficient and wild type (WT) littermate controls underwent bilateral renal ischaemia/reperfusion injury (IRI) and were killed 24 h later or underwent left unilateral ureteric obstruction (UUO) and were killed 7 days later. In the IRI model, <i>CypA<sup>−/−</sup></i> 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 <i>CypA<sup>−/−</sup></i> tubular cells were not protected from oxidant-induced cell death in vitro. In the UUO model, <i>CypA<sup>−/−</sup></i> 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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spelling doaj.art-1d1b9603b7204caaa7623271036bda972023-11-20T01:24:19ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-05-012110366710.3390/ijms21103667Cyclophilin A Promotes Inflammation in Acute Kidney Injury but Not in Renal FibrosisKhai Gene Leong0Elyce Ozols1John Kanellis2David J. Nikolic-Paterson3Frank Y. Ma4Department of Nephrology, Monash Health, Monash Medical Centre, Clayton, Victoria 3168, AustraliaDepartment of Nephrology, Monash Health, Monash Medical Centre, Clayton, Victoria 3168, AustraliaDepartment of Nephrology, Monash Health, Monash Medical Centre, Clayton, Victoria 3168, AustraliaDepartment of Nephrology, Monash Health, Monash Medical Centre, Clayton, Victoria 3168, AustraliaDepartment of Nephrology, Monash Health, Monash Medical Centre, Clayton, Victoria 3168, AustraliaCyclophilin 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. <i>CypA (Ppia)</i> gene deficient and wild type (WT) littermate controls underwent bilateral renal ischaemia/reperfusion injury (IRI) and were killed 24 h later or underwent left unilateral ureteric obstruction (UUO) and were killed 7 days later. In the IRI model, <i>CypA<sup>−/−</sup></i> 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 <i>CypA<sup>−/−</sup></i> tubular cells were not protected from oxidant-induced cell death in vitro. In the UUO model, <i>CypA<sup>−/−</sup></i> 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.https://www.mdpi.com/1422-0067/21/10/3667acute kidney injurychronic kidney diseasecyclophilin Afibrosisinflammationrenal fibrosis
spellingShingle Khai Gene Leong
Elyce Ozols
John Kanellis
David J. Nikolic-Paterson
Frank Y. Ma
Cyclophilin A Promotes Inflammation in Acute Kidney Injury but Not in Renal Fibrosis
International Journal of Molecular Sciences
acute kidney injury
chronic kidney disease
cyclophilin A
fibrosis
inflammation
renal fibrosis
title Cyclophilin A Promotes Inflammation in Acute Kidney Injury but Not in Renal Fibrosis
title_full Cyclophilin A Promotes Inflammation in Acute Kidney Injury but Not in Renal Fibrosis
title_fullStr Cyclophilin A Promotes Inflammation in Acute Kidney Injury but Not in Renal Fibrosis
title_full_unstemmed Cyclophilin A Promotes Inflammation in Acute Kidney Injury but Not in Renal Fibrosis
title_short Cyclophilin A Promotes Inflammation in Acute Kidney Injury but Not in Renal Fibrosis
title_sort cyclophilin a promotes inflammation in acute kidney injury but not in renal fibrosis
topic acute kidney injury
chronic kidney disease
cyclophilin A
fibrosis
inflammation
renal fibrosis
url https://www.mdpi.com/1422-0067/21/10/3667
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AT johnkanellis cyclophilinapromotesinflammationinacutekidneyinjurybutnotinrenalfibrosis
AT davidjnikolicpaterson cyclophilinapromotesinflammationinacutekidneyinjurybutnotinrenalfibrosis
AT frankyma cyclophilinapromotesinflammationinacutekidneyinjurybutnotinrenalfibrosis