Inhibition of Peptidyl Arginine Deiminase-4 Prevents Renal Ischemia-Reperfusion-Induced Remote Lung Injury

Joint Authors

Yang, Lei
Wu, Jiawei
Du, Mingjun
Gu, Jianmin
Ma, Yiwen
Wang, Tao

Source

Mediators of Inflammation

Issue

Vol. 2020, Issue 2020 (31 Dec. 2020), pp.1-14, 14 p.

Publisher

Hindawi Publishing Corporation

Publication Date

2020-12-30

Country of Publication

Egypt

No. of Pages

14

Main Topic

Diseases

Abstract EN

Ischemia reperfusion (IR) can lead to acute kidney injury and can be complicated by acute lung injury, which is one of the leading causes of acute kidney injury-related death.

Peptidyl arginine deiminase-4 (PAD4) is a member of the PAD enzyme family and plays a critical role in inflammatory reactions and neutrophil extracellular trap formation in a variety of pathological conditions.

It has been reported that PAD4 inhibition can protect certain organs from ischemic injury.

In this study, we aimed to understand the mode of action of PAD4 in renal ischemia-reperfusion-mediated acute lung injury.

Bilateral renal pedicle occlusion was induced for 30 min followed by reperfusion for 24 h.

A specific inhibitor of PAD4, GSK484, was delivered via intraperitoneal injection to alter the PAD4 activity.

The pulmonary PAD4 expression, pulmonary impairment, neutrophil infiltration, Cit-H3 expression, neutrophil extracellular trap formation, inflammatory cytokine secretion, and pulmonary apoptosis were analyzed.

We found that renal ischemia reperfusion was associated with pulmonary pathological changes and increases in neutrophil infiltration, neutrophil extracellular trap formation, and inflammatory cytokine secretion in the lungs of the recipient animals.

Suppression of PAD4 by GSK484 reduced remote lung injury by mitigating neutrophil infiltration, neutrophil extracellular trap formation, apoptosis, and inflammatory factor secretion.

Our findings demonstrate that specific PAD4 inhibition by GSK484 may be an effective strategy to attenuate distant lung injury complicating renal ischemia-reperfusion injury.

American Psychological Association (APA)

Du, Mingjun& Yang, Lei& Gu, Jianmin& Wu, Jiawei& Ma, Yiwen& Wang, Tao. 2020. Inhibition of Peptidyl Arginine Deiminase-4 Prevents Renal Ischemia-Reperfusion-Induced Remote Lung Injury. Mediators of Inflammation،Vol. 2020, no. 2020, pp.1-14.
https://search.emarefa.net/detail/BIM-1191531

Modern Language Association (MLA)

Du, Mingjun…[et al.]. Inhibition of Peptidyl Arginine Deiminase-4 Prevents Renal Ischemia-Reperfusion-Induced Remote Lung Injury. Mediators of Inflammation No. 2020 (2020), pp.1-14.
https://search.emarefa.net/detail/BIM-1191531

American Medical Association (AMA)

Du, Mingjun& Yang, Lei& Gu, Jianmin& Wu, Jiawei& Ma, Yiwen& Wang, Tao. Inhibition of Peptidyl Arginine Deiminase-4 Prevents Renal Ischemia-Reperfusion-Induced Remote Lung Injury. Mediators of Inflammation. 2020. Vol. 2020, no. 2020, pp.1-14.
https://search.emarefa.net/detail/BIM-1191531

Data Type

Journal Articles

Language

English

Notes

Includes bibliographical references

Record ID

BIM-1191531