ArticleJournal of the American Society of Nephrology : JASN2010
HSP72 inhibits Smad3 activation and nuclear translocation in renal epithelial-to-mesenchymal transition.
Article in Journal of the American Society of Nephrology : JASN, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 33 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
33 citing papers in PubMed, 65 citations in OpenAlex.
- Silencing METTL3 Increases HSP70 Expression and Alleviates Fibrosis in Keratocytes.Investigative ophthalmology & visual science · 2024Article
- Emetine dihydrochloride alleviated radiation-induced lung injury through inhibiting EMT.Journal of cellular and molecular medicine · 2023Article
- Downregulation of Heat Shock Protein 72 Contributes to Fibrostenosis in Crohn's Disease.Gut and liver · 2023Article
- HSP70 Family in Cancer: Signaling Mechanisms and Therapeutic Advances.Biomolecules · 2023Review
- APOBEC1 complementation factor facilitates cell migration by promoting nucleus translocation of SMAD3 in renal cell carcinoma cells.In vitro cellular & developmental biology. Animal · 2021Article
- The Role of TGF-Evidence-based complementary and alternative medicine : eCAM · 2021Review
- Expression correlation attenuates within and between key signaling pathways in chronic kidney disease.BMC medical genomics · 2020Article
- Article
- Triptolide inhibits migration and proliferation of fibroblasts from ileocolonic anastomosis of patients with Crohn's disease via regulating the miR‑16‑1/HSP70 pathway.Molecular medicine reports · 2019Article
- Natural Plants Compounds as Modulators of Epithelial-to-Mesenchymal Transition.Frontiers in pharmacology · 2019Review
- Cryptotanshinone hinders renal fibrosis and epithelial transdifferentiation in obstructive nephropathy by inhibiting TGF-β1/Smad3/integrin β1 signal.Oncotarget · 2018Article
- Acetylation of HMGB1 by JNK1 Signaling Promotes LPS-Induced Peritoneal Mesothelial Cells Apoptosis.BioMed research international · 2018Article
- Triptolide exerts protective effects against fibrosis following ileocolonic anastomosis by mechanisms involving the miR-16-1/HSP70 pathway in IL-10-deficient mice.International journal of molecular medicine · 2017Article
- Macrophage-to-Myofibroblast Transition Contributes to Interstitial Fibrosis in Chronic Renal Allograft Injury.Journal of the American Society of Nephrology : JASN · 2017Article
- Heat shock proteins and kidney disease: perspectives of HSP therapy.Cell stress & chaperones · 2017Review
- Mild electrical stimulation with heat shock guides differentiation of embryonic stem cells into Pdx1-expressing cells within the definitive endoderm.BMC biotechnology · 2017Article
- Growing evidence suggests WT1 effects in the kidney development are modulated by Hsp70/NO interaction.Journal of nephrology · 2017Review
- Detainment of Tam3 Transposase at Plasma Membrane by Its BED-Zinc Finger Domain.Plant physiology · 2017Article
- The Human Amnion Epithelial Cell Secretome Decreases Hepatic Fibrosis in Mice with Chronic Liver Fibrosis.Frontiers in pharmacology · 2017Article
- Hydroxysafflor Yellow A Ameliorates Renal Fibrosis by Suppressing TGF-β1-Induced Epithelial-to-Mesenchymal Transition.PloS one · 2016Article
Corrections and comments
- Erratum issued
Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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-beta signaling from the cytosol to the nucleus and HSP72 assists in protein folding and facilitates nuclear translocation, we investigated whether HSP72 inhibits TGF-beta-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-DeltaPBD), which is responsible for substrate binding and refolding, or the nuclear localization signal (HSP72-DeltaNLS). Overexpression of wild-type HSP72 or HSP72-DeltaNLS inhibited TGF-beta1-induced EMT, but HSP72-DeltaPBD did not, suggesting a critical role for the PBD in this inhibition. HSP72 overexpression inhibited TGF-beta1-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-beta1-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.
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