Heat Shock Factor Network in Kidney Diseases
Introduction Heat shock response (HSR) pathway is a highly conserved cellular process. HSF1 is a master transcriptional regulator responsible for expression of several important heat shock proteins (HSP), which can effectively protect critical client prot
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Abstract Introduction Heat shock response (HSR) pathway is a highly conserved cellular process. HSF1 is a master transcriptional regulator responsible for expression of several important heat shock proteins (HSP), which can effectively protect critical client proteins from misfolding and degradation, thus maintaining intracellular integrity under stressed conditions. Recent studies have demonstrated the direct connections between HSR players and tumor cell survival, validating HSR players as novel molecular targets in anticancer treatment. Small molecule screening has produced some promising HSR inhibitors for anticancer treatment. In this article, we will be summarizing the main findings from HSR inhibitors on recent clinical and preclinical studies. Methods The authors reviewed all the relevant papers of HSR inhibitors with an emphasis on human and animal studies. Results More than 18 unique chemical identities have been discovered with confirmed inhibition of HSR pathway. Among them, two natural products and their derivatives are currently in various phases of clinical studies. Detailed works are required to define the exact mechanisms of actions (MOA) for these compounds. Conclusions Many hurdles in clinical application still need to be effectively addressed, such as undesirable drug toxicity and off target effects; narrow therapeutic window; poor PK/PD profiles, etc. Recent reports on synergistic drug combination, advanced prodrug design, smart nanoparticle packaging, and RNA aptamer selection offer promising solutions to overcome these challenges. Future advancements in this fast-growing area can potentially lead to the next-generation cancer therapeutics.
K. Musiał (*) · D. Zwolińska Department of Pediatric Nephrology, Wrocław Medical University, Wrocław, Poland e-mail: [email protected] © Springer Nature Switzerland AG 2020 A. A. A. Asea, P. Kaur (eds.), Heat Shock Proteins, https://doi.org/10.1007/7515_2020_30
K. Musiał and D. Zwolińska
Keywords Acute kidney injury · Chronic kidney disease · Heat shock factor 1 · Heat shock protein · Ischemia reperfusion injury · Tubular function
Abbreviations AMPK ATP ccRCC CKD CR+/CRCryAB FE GBM HBA HD HIF1 HO HSE HSF Hsf1 Hsf1-M30 HSF-KO Hsf1 KD cells Hsf1 NC cells HSP Hsp25 KIM-1 LDH M30 PGC1α PFP PTM RBP-4 RPTC S1R TGF-β1 TTR+/TTRTTRV30M VDBP WT
50 adenosine monophosphate-activated protein kinase 50 adenosine triphosphate clear cell renal cell carcinoma chronic kidney disease presence/absence of glomerular amyloid deposition by the Congo Red staining crystallin-αB fractional excretion glomerular basement membrane Hsp90-binding agent hemodialysis hypoxia-inducible factor 1 heme-oxygenase heat shock element heat shock factors heat shock factor 1 Hsf1 hemizygous mice Hsf1 functional knockout mice Hsf1 knockdown rat proximal tubular cells rat proximal tubular negative control cells heat shock proteins heat shock protein 25 kidney injury molecule-1 lactate dehydrogenase Hsf-1 homozygous mice peroxisome proliferator-activated receptor-γ coactivator 1 α podocyte foot
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