HSP72 attenuates renal tubular cell apoptosis and interstitial fibrosis in obstructive nephropathy

Mao, Haiping; Li, Zhilian; Zhou, Yi; Z, Li; Zhuang, Songlin; An, Xiaopeng; Bai-yu, Zhang; Chen, Wei; Nie, Jing; Wang, Zhiyong; Borkan, Steven C.; Wang, Yihan; Yu, Xueqing

doi:10.1152/ajprenal.00468.2007

Cited by 92 publications

(102 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Therefore, the interpretation of adaptive response in the course of CKD should be viewed cautiously. Mao et al [15] studied the impact of HSP on chronic kidney damage in rats with obstructive uropathy. The selective activation of HSP 72 given orally inhibited the proliferation an apoptosis in tubular cells and diminished the accumulation of fibroblasts and collagen-1 generation in renal parenchymal cells, thus slowing the process of fibrosis.…”

Section: Role Of Hsp In Chronic Kidney Diseasementioning

confidence: 99%

The role of heat shock proteins in kidney disease

Rao

2016

Journal of Translational Internal Medicine

View full text Add to dashboard Cite

Heat Shock Proteins (HSP) belong to the family of intracellular proteins that are constitutively expressed and are upregulated by various stressors including heat, oxidative and chemical stress. HSP helps in reparative processes, including the refolding of damaged proteins and the removal of irreparably damaged proteins that would initiate cellular death or apoptosis. A growing body of evidence has expanded the role of HSP and defined their role in diseases such as neurodegenerative disorders, cancer, ischemic heart disease and kidney diseases. The protective role of HSP in ischemic renal injury has been described and HSP impairment has been noted in other forms of kidney injuries including post-transplant situation. Further research into the role of HSP in prevention of kidney injury is crucial if translation from the laboratory to patient bedside has to occur. This article aims to be a review of heat shock protein, and its relevance to kidney diseases.

show abstract

Section: Role Of Hsp In Chronic Kidney Diseasementioning

confidence: 99%

The role of heat shock proteins in kidney disease

Rao

2016

Journal of Translational Internal Medicine

View full text Add to dashboard Cite

show abstract

“…10 To study the role of HSP72 in regulating EMT, NRK-52E cells were transiently and individually transfected with plasmid vectors encoding HA-epitope tagged-Wt-HSP72, HA-HSP72-⌬PBD, or HA-HSP72-⌬NLS ( Figure 1A), and pcDNA3.1-HA empty vector was used as control. Previously characterized human kidney proximal tubule cells (HK-2) in which endogenous HSP72 is readily detected was used as an additional control.…”

Section: Expression Of Wt-hsp72 and Hsp72 Mutants And Hsp72 Sirna Knomentioning

confidence: 99%

“…10 To evaluate whether HSP72 plays a role in the regulation of Smad signaling in vivo, we examined Smad proteins at 7 days after UUO. UUO induced Smad2 and Smad3 phosphorylation and reduced Smad7 content compared with sham controls.…”

Section: Hsp72 Blocks Smad Signaling In the Obstructed Kidney Inducedmentioning

confidence: 99%

“…8,9 However, some cytoprotective effects do not require the HSP72 chaperone function. 10 HSP72 contains distinct domains: a C-terminal peptide-binding domain (PBD) responsible for substrate binding and refolding, and a nuclear localization signal (NLS) that regulates HSP72 nuclear accumulation under stress conditions. 11,12 It is evident that the PBD of HSP72 prevents apoptosis by inhibiting Bax activation, preventing mitochondrial cytochrome c and apoptosis-inducing factor release and subsequent caspase activation.…”

mentioning

confidence: 99%

“…10 However, the mechanisms by which HSP72 regulates EMT have not been determined. Because Smad3 transduces TGF-␤ signaling from the cytosol to the nucleus, 6 and HSP72 acts as a chaperone that facilitates the movement of proteins across the nuclear membrane, 13,19,20 we hypothesized that HSP72 inhibits TGF-␤-induced EMT by interrupting Smad protein phosphorylation and its nuclear translocation and accumulation.…”

mentioning

confidence: 99%

See 2 more Smart Citations

HSP72 Inhibits Smad3 Activation and Nuclear Translocation in Renal Epithelial-to-Mesenchymal Transition

Zhou¹,

Mao²,

Li³

et al. 2010

Journal of the American Society of Nephrology

Self Cite

View full text Add to dashboard Cite

Although heat shock protein 72 (HSP72) ameliorates renal tubulointerstitial fibrosis by inhibiting epithelial-to-mesenchymal transition (EMT), the underlying mechanism is unknown. Because Smad proteins transduce TGF-␤ signaling from the cytosol to the nucleus and HSP72 assists in protein folding and facilitates nuclear translocation, we investigated whether HSP72 inhibits TGF-␤-induced EMT by modulating Smad expression, activation, and nuclear translocation. To evaluate the roles of distinct HSP72 structural domains in these processes, we constructed vectors that expressed wild-type HSP72 or mutants lacking either the peptide-binding domain (HSP72-⌬PBD), which is responsible for substrate binding and refolding, or the nuclear localization signal (HSP72-⌬NLS). Overexpression of wild-type HSP72 or HSP72-⌬NLS inhibited TGF-␤1-induced EMT, but HSP72-⌬PBD did not, suggesting a critical role for the PBD in this inhibition. HSP72 overexpression inhibited TGF-␤1-induced phosphorylation and nuclear translocation of Smad3 and p-Smad3, but not Smad2; these inhibitory effects required the PBD but not the NLS. Coimmunoprecipitation assays suggested a physical interaction between Smad3 and the PBD. siRNA knockdown of endogenous HSP72 enhanced both TGF-␤1-induced Smad3 phosphorylation and EMT and confirmed the interaction of HSP72 with both Smad3 and p-Smad3. In vivo, induction of HSP72 by geranylgeranylacetone suppressed Smad3 phosphorylation in renal tubular cells after unilateral ureteral obstruction. In conclusion, HSP72 inhibits EMT in renal epithelial cells primarily by exerting domain-specific effects on Smad3 activation and nuclear translocation. 21: 598 -609, 201021: 598 -609, . doi: 10.1681 Transforming growth factor ␤ (TGF-␤) and related factors regulate a wide variety of biologic activities. 1 Furthermore, abnormalities in TGF-␤ signaling lead to various human diseases. 2 Signals from TGF-␤ are mainly transduced by the Smad family of transcription factors. Upon TGF-␤ stimulation, Smad2 and Smad3 are phosphorylated at their carboxy-tails by the activated TGF-␤ type I receptor kinase, 3 forming a stable complex with Smad4 in cytoplasm and then accumulating in the nucleus to regulate transcription of target genes. In contrast, Smad7 inhibits the TGF-␤ receptor type I-dependent Smad2/3 activation. It has been demonstrated that Smad3 phosphorylation plays a predominant role in guiding the complex through the nuclear pore. 4 cytoplasm. 5 Blockade of TGF-␤ signaling events, specifically the phosphorylation of Smad2 and Smad3 and/or nuclear translocation, prevent epithelial-to-mesenchymal transition (EMT) and tissue fibrosis. 6,7 Heat shock protein 72 (HSP72) exerts cytoprotective effects by assisting in protein folding, assembly/disassembly and translocation of client proteins across membranes, protein degradation, and signal transduction. 8,9 However, some cytoprotective effects do not require the HSP72 chaperone function. 10 HSP72 contains distinct domains: a C-terminal peptide-binding domain (PBD) responsible...

show abstract

Epithelial‐To‐Mesenchymal Transition: Immunohistochemical Investigation of Related Molecules in Canine Cutaneous Epithelial Tumours

Bongiovanni

D'Andrea

Romanucci

et al. 2013

Advances in Veterinary Dermatology

View full text Add to dashboard Cite

HSP72 attenuates renal tubular cell apoptosis and interstitial fibrosis in obstructive nephropathy

Abstract: X. HSP72 attenuates renal tubular cell apoptosis and interstitial fibrosis in obstructive nephropathy.

Cited by 92 publications

References 53 publications

The role of heat shock proteins in kidney disease

The role of heat shock proteins in kidney disease

HSP72 Inhibits Smad3 Activation and Nuclear Translocation in Renal Epithelial-to-Mesenchymal Transition

Epithelial‐To‐Mesenchymal Transition: Immunohistochemical Investigation of Related Molecules in Canine Cutaneous Epithelial Tumours

Contact Info

Product

Resources

About