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2016 ; 7
(34
): 54290-54302
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NLRP3 inflammasome activation is involved in Ang II-induced kidney damage via
mitochondrial dysfunction
#MMPMID27509058
Wen Y
; Liu Y
; Tang T
; Lv L
; Liu H
; Ma K
; Liu B
Oncotarget
2016[Aug]; 7
(34
): 54290-54302
PMID27509058
show ga
Growing evidence has shown that NLRP3 inflammasome activation promotes the
development of tubularinterstitial inflammation and progression of renal injury.
We previously found that mitochondrial dysfunction is a critical determinant for
the activation of NLRP3 inflammasome in albumin-overload rats. Angiotensin (Ang)
II plays an important role in mitochondrial homeostasis. Here, we investigated
the role of Ang II in NLRP3 inflammasome activation and the involvement of
mitochondrial dysfunction in this process. In vitro, Ang II triggered NLRP3
inflammasome activation in a dose- and time-dependent manner, and this effect is
mediated by AT1 receptor rather than AT2 receptor. MitoTEMPO, a mitochondrial
targeted antioxidant, attenuated Ang II induced mitochondrial reactive oxygen
species (mROS) production and NLRP3 inflammation activation. Following chronic
Ang II infusion for 28 days, we observed remarkable tubular epithelial cells
(TECs) injury, mitochondrial damage, and albuminuria in WT mice. However, these
abnormalities were significantly attenuated in AT1 receptor KO mice. Then, we
examined the role of mitochondria in Ang II-infused mice with or without
mitoTEMPO treatment. As expected, Ang II-induced mitochondrial dysfunction and
NLRP3 inflammasome activation was markedly inhibited by mitoTEMPO. Notably, NLRP3
deletion signally protected TECs from Ang II-triggered mitochondrial dysfunction
and NLRP3 inflammasome activation. Taken together, these data demonstrate that
Ang II induces NLRP3 inflammasome activation in TECs which is mediated by
mitochondrial dysfunction.