CKIP-1 affects the polyubiquitination of Nrf2 and Keap1 via mediating Smurf1 to resist HG-induced renal fibrosis in GMCs and diabetic mice kidneys

Gong, Wenyan; Chen, Zhiquan; Zou, Yao; Zhang, Lei; Huang, Junying; Liu, Peiqing; Huang, Heqing

doi:10.1016/j.freeradbiomed.2017.12.013

Cited by 47 publications

(26 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our results indicated that activation of Nrf2 / ARE signaling pathway might help to prevent DR progression, which was in compliance with the previous study [34]. Notably, previous studies have proved that Nrf2 / ARE signaling pathway was the downstream target and could be activated by CKIP - 1 overexpression [11, 18, 27, 35]. However, it is still unclear whether CKIP - 1 alleviates DR development by regulating Nrf2 / ARE signaling pathway.…”

Section: Discussionsupporting

confidence: 92%

“…CKIP - 1 has been reported to regulate multiple cell functions (cell proliferation [9, 10], apoptosis [11] and differentiation [26]) and involve in the development of several diseases including renal fibrosis [27], chronic heart failure [28], cancer [29] and so on. Recent studies also found that inflammation [12, 13] and oxidative stress [11] could be regulated by CKIP - 1 .…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Upregulation of CKIP-1 inhibits high-glucose induced inflammation and oxidative stress in HRECs and attenuates diabetic retinopathy by modulating Nrf2/ARE signaling pathway: an in vitro study

Zhang

et al. 2019

Cell Biosci

View full text Add to dashboard Cite

Purpose The aim of this study was to investigate the underlying mechanisms of diabetic retinopathy (DR) development. Methods Real-Time qPCR was used to detect Casein kinase 2 interacting protein - 1 ( CKIP - 1 ) and Nuclear factor E2 - related factor 2 ( Nrf2 ) mRNA levels. Western Blot was employed to detect protein levels. Malondialdehyde (MDA) assay kit, superoxide dismutase (SOD) kit and glutathione peroxidase (GSH-Px) kit were used to evaluate oxidative stress in high-glucose treated human retinal endothelial cells (HRECs). Calcein-AM/propidium iodide (PI) double stain kit was employed to detect cell apoptosis. Enzyme-linked ImmunoSorbent Assay (ELISA) was used to detect inflammation associated cytokines secretion. Co-immunoprecipitation (CO-IP) was performed to investigate the interactions between CKIP - 1 and Nrf2 . Luciferase reporter gene system was used to detect the transcriptional activity of Nrf2 . Results CKIP - 1 was significantly downregulated in either DR tissues or high-glucose treated HRECs comparing to the Control groups. Besides, high-glucose (25 mM) inhibited HRECs viability and induced oxidative stress, inflammation associated cytokines (TNF-α, IL-6 and IL-1β) secretion and cell apoptosis, which were all reversed by synergistically overexpressing CKIP - 1 and aggravated by knocking down CKIP - 1 . Of note, we found that overexpressed CKIP - 1 activated Nrf2 / ARE signaling pathway and increased its downstream targets including HO - 1 , NQO - 1 , γGCS and SOD in high-glucose treated HRECs. Further results also showed that CKIP - 1 regulated cell viability, oxidative stress, inflammation and apoptosis in high-glucose treated HRECs by activating Nrf2 / ARE signaling pathway. Conclusion We concluded that overexpressed CKIP - 1 alleviated DR progression by activating Nrf2 / ARE signaling pathway.

show abstract

Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Upregulation of CKIP-1 inhibits high-glucose induced inflammation and oxidative stress in HRECs and attenuates diabetic retinopathy by modulating Nrf2/ARE signaling pathway: an in vitro study

Zhang

et al. 2019

Cell Biosci

View full text Add to dashboard Cite

show abstract

“…Directly destroying the combination of Nrf2-Keap1 complex has been proved to be effective as a novel Nrf2 activation strategy (L. Zhou et al, 2015). Our group have previously confirmed that CKIP-1 interacted with Nrf2 in GMCs, and CKIP-1 could affect the polyubiquitination of Nrf2 and Keap1 by regulating Smurf1 to activate the Nrf2 signaling pathway (W. Gong et al, 2018).On this basis, we mainly explored the molecular mechanism by which Cx43 mediated the activation of the Nrf2 pathway by regulating CKIP-1 in the present study.…”

Section: Discussionmentioning

confidence: 62%

CKIP-1 participates in the activation of Nrf2 signaling pathway by Cx43 and the regulation of diabetic renal fibrosis

Huang¹,

Yang²,

Lin³

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

Background and Purpose We previously reported that both Cx43 and CKIP-1 attenuated diabetic renal fibrosis via the activation of Nrf2 signaling pathway. However, whether CKIP-1, a scaffold protein, participates in regulating the activation of Nrf2 signaling pathway by Cx43 remains to be elucidated. Experimental Approach The effect of adenovirus-mediated Cx43 overexpression on renal fibrosis in CKIP-1-/-diabetic mice was investigated. Cx43 overexpressed plasmid and CKIP-1 small interfering RNA were simultaneously transfected into GMCs and the activity of Nrf2 signaling pathway was observed. The interaction between Cx43 and CKIP-1 was analyzed by immunofluorescence and immunoprecipitation assays. Key Results Overexpression of Cx43 could significantly alleviate renal fibrosis by activating the Nrf2 pathway in diabetic mice, but have no obvious effect in CKIP-1-/-diabetic mice. The effect of activation of Nrf2 signaling pathway by Cx43 was blocked by CKIP-1 depletion. Cx43 interacted with CKIP-1, and the interaction was weakened by high glucose treatment. Cx43 regulated the expression of CKIP-1 and the interaction of CKIP-1 with Nrf2 via Cx43 carboxyl terminus (CT) domain, thereby activating Nrf2 signaling pathway. Conclusion and Implications CKIP-1 participates in regulating the activation of Nrf2 signaling pathway by Cx43, the mechanism of which might be related to the interaction of CKIP-1 with Nrf2 through Cx43 CT. Our study provides further experimental basis for targeting the Cx43-CKIP-1-Nrf2 axis to resist diabetic renal fibrosis. Background and Purpose We previously reported that both Cx43 and CKIP-1 attenuated diabetic renal fibrosis via the activation of Nrf2 signaling pathway. However, whether CKIP-1, a scaffold protein, participates in regulating the activation of Nrf2 signaling pathway by Cx43 remains to be elucidated. Experimental Approach The effect of adenovirus-mediated Cx43 overexpression on renal fibrosis in CKIP-1-/diabetic mice was investigated. Cx43 overexpressed plasmid and CKIP-1 small interfering RNA were simultaneously transfected into GMCs and the activity of Nrf2 signaling pathway was observed. The interaction between Cx43 and CKIP-1 was analyzed by immunofluorescence and immunoprecipitation assays. Key Results Overexpression of Cx43 could significantly alleviate renal fibrosis by activating the Nrf2 pathway in diabetic mice, but have no obvious effect in CKIP-1-/diabetic mice. The effect of activation of Nrf2 signaling pathway by Cx43 was blocked by CKIP-1 depletion. Cx43 interacted with CKIP-1, and the interaction was weakened by high glucose treatment. Cx43 regulated the expression of CKIP-1 and the interaction of CKIP-1 with Nrf2 via Cx43 carboxyl terminus (CT) domain, thereby activating Nrf2 signaling pathway.

show abstract

“…Firstly, SMURF1 activates SMAD-dependent EMT signalling by blocking SMAD7, the SMAD2/3 inhibitor [230] (Section 3.2). Furthermore, SMURF1 has been discovered to decrease the expression and nuclear translocation of NRF2L2, thus down-regulating the KEAP1-NFE2L2 pathway [234]. Casein kinase 2 interacting protein-1 (CKIP-1) has been reported to be a direct down-regulator of SMURF1.…”

Section: Epithelial To Mesenchymal Transition (Emt)mentioning

confidence: 99%

“…CKIP-1 is inducible in OS, caused by oxygen-glucose deprivation/reoxygenation (i.e. conditions encountered in hypoxia) [234,235]. As far as we are aware, ROS themselves have not been reported to be connected to the activation of CKIP-1.…”

Section: Epithelial To Mesenchymal Transition (Emt)mentioning

confidence: 99%

The Regulation of NFE2L2 (NRF2) Signalling and Epithelial-to-Mesenchymal Transition in Age-Related Macular Degeneration Pathology

Hyttinen

Kannan

Felszeghy

et al. 2019

IJMS

View full text Add to dashboard Cite

Age-related macular degeneration (AMD) is a mounting cause of loss of sight in the elderly in the developed countries, a trend enhanced by the continual ageing of the population. AMD is a multifactorial and only partly understood, malady. Unfortunately, there is no effective treatment for most AMD patients. It is known that oxidative stress (OS) damages the retinal pigment epithelium (RPE) and contributes to the progression of AMD. We review here the potential importance of two OS-related cellular systems in relation to AMD. First, the nuclear factor erythroid 2-related factor 2 (NFE2L2; NRF2)-mediated OS response signalling pathway is important in the prevention of oxidative damage and a failure of this system could be critical in the development of AMD. Second, epithelial-to-mesenchymal transition (EMT) represents a change in the cellular phenotype, which ultimately leads to the fibrosis encountered in RPE, a characteristic of AMD. Many of the pathways triggering EMT are promoted by OS. The possible interconnections between these two signalling routes are discussed here. From a broader perspective, the control of NFE2L2 and EMT as ways of preventing OS-derived cellular damage could be potentially valuable in the therapy of AMD.

show abstract

CKIP-1 affects the polyubiquitination of Nrf2 and Keap1 via mediating Smurf1 to resist HG-induced renal fibrosis in GMCs and diabetic mice kidneys

Cited by 47 publications

References 43 publications

Upregulation of CKIP-1 inhibits high-glucose induced inflammation and oxidative stress in HRECs and attenuates diabetic retinopathy by modulating Nrf2/ARE signaling pathway: an in vitro study

Upregulation of CKIP-1 inhibits high-glucose induced inflammation and oxidative stress in HRECs and attenuates diabetic retinopathy by modulating Nrf2/ARE signaling pathway: an in vitro study

CKIP-1 participates in the activation of Nrf2 signaling pathway by Cx43 and the regulation of diabetic renal fibrosis

The Regulation of NFE2L2 (NRF2) Signalling and Epithelial-to-Mesenchymal Transition in Age-Related Macular Degeneration Pathology

Contact Info

Product

Resources

About