TY - JOUR
T1 - Peroxiredoxin 3 deficiency accelerates chronic kidney injury in mice through interactions between macrophages and tubular epithelial cells
AU - Hwang, Inah
AU - Uddin, Md Jamal
AU - Lee, Gayoung
AU - Jiang, Songling
AU - Pak, Eun Seon
AU - Ha, Hunjoo
N1 - Funding Information:
This work was supported by a National Research Foundation grant (No. 2016R1A2B4006575 ) and Korean Research Fellowship Program (No. 2015H1D3A1062189 ), Republic of Korea.
Funding Information:
This work was supported by a National Research Foundation grant (No. 2016R1A2B4006575) and Korean Research Fellowship Program (No. 2015H1D3A1062189), Republic of Korea.
Publisher Copyright:
© 2018 Elsevier Inc.
PY - 2019/2/1
Y1 - 2019/2/1
N2 - Chronic kidney disease (CKD) has become epidemic worldwide. Mitochondrial reactive oxygen species (ROS)-induced oxidative stress is an important mediator of CKD, and Prx3 plays a critical role in maintenance of mitochondrial ROS. The present study examined the role of Prx3 in the context of fibrosis, a common feature of CKD, using Prx3 KO mice under obstructive and diabetic stress. Prx3 deficiency accelerated fibrosis and inflammation accompanied by mitochondrial oxidative stress in obstructed and diabetic kidneys as well as in proximal tubular epithelial (mProx) cells. In addition, Prx3 deficiency induced Raw264.7 macrophages activation, leading to upregulation of proinflammatory cytokines. Conditioned media from LPS-stimulated Prx3 deficient macrophages accelerated proinflammatory and profibrotic cytokines in mProx cells. Interestingly, Prx3 deficiency induced most inflammatory and fibrotic cytokines at basal condition in both tissues and cells. Taken together, these results demonstrate that Prx3 deficiency can accelerate CKD through interactions between macrophages and tubular epithelial cells.
AB - Chronic kidney disease (CKD) has become epidemic worldwide. Mitochondrial reactive oxygen species (ROS)-induced oxidative stress is an important mediator of CKD, and Prx3 plays a critical role in maintenance of mitochondrial ROS. The present study examined the role of Prx3 in the context of fibrosis, a common feature of CKD, using Prx3 KO mice under obstructive and diabetic stress. Prx3 deficiency accelerated fibrosis and inflammation accompanied by mitochondrial oxidative stress in obstructed and diabetic kidneys as well as in proximal tubular epithelial (mProx) cells. In addition, Prx3 deficiency induced Raw264.7 macrophages activation, leading to upregulation of proinflammatory cytokines. Conditioned media from LPS-stimulated Prx3 deficient macrophages accelerated proinflammatory and profibrotic cytokines in mProx cells. Interestingly, Prx3 deficiency induced most inflammatory and fibrotic cytokines at basal condition in both tissues and cells. Taken together, these results demonstrate that Prx3 deficiency can accelerate CKD through interactions between macrophages and tubular epithelial cells.
KW - CKD
KW - Macrophage activation
KW - Oxidative stress
KW - Prx3 deficiency
UR - http://www.scopus.com/inward/record.url?scp=85058046782&partnerID=8YFLogxK
U2 - 10.1016/j.freeradbiomed.2018.12.002
DO - 10.1016/j.freeradbiomed.2018.12.002
M3 - Article
C2 - 30529270
AN - SCOPUS:85058046782
SN - 0891-5849
VL - 131
SP - 162
EP - 172
JO - Free Radical Biology and Medicine
JF - Free Radical Biology and Medicine
ER -
