ArticleThe Journal of biological chemistry2014
No amelioration of uromodulin maturation and trafficking defect by sodium 4-phenylbutyrate in vivo: studies in mouse models of uromodulin-associated kidney disease.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 24 citations in OpenAlex.
- Advances in uromodulin biology and potential clinical applications.Nature reviews. Nephrology · 2024Review
- Clinical and genetic spectra of autosomal dominant tubulointerstitial kidney disease.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2023Article
- Phenylbutyrate rescues the transport defect of the Sec61α mutations V67G and T185A for renin.Life science alliance · 2022Article
- Familial juvenile hyperuricemia in early childhood in a boy with a novel gene mutation.CEN case reports · 2021Article
- Chemical chaperone treatment improves levels and distributions of connexins in Cx50D47A mouse lenses.Experimental eye research · 2018Article
- Endoplasmic reticulum stress, the unfolded protein response and autophagy in kidney diseases.Nature reviews. Nephrology · 2017Review
- Uromodulin: from physiology to rare and complex kidney disorders.Nature reviews. Nephrology · 2017Review
- Early involvement of cellular stress and inflammatory signals in the pathogenesis of tubulointerstitial kidney disease due to UMOD mutations.Scientific reports · 2017Article
- Mitochondrial Dysregulation Secondary to Endoplasmic Reticulum Stress in Autosomal Dominant Tubulointerstitial Kidney Disease - UMOD (ADTKD-UMOD).Scientific reports · 2017Article
- Mutant uromodulin expression leads to altered homeostasis of the endoplasmic reticulum and activates the unfolded protein response.PloS one · 2017Article
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Authors and funding
7 authors at 2 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
Uromodulin (UMOD)-associated kidney disease (UAKD) belongs to the hereditary progressive ER storage diseases caused by maturation defects of mutant UMOD protein. Current treatments of UAKD patients are symptomatic and cannot prevent disease progression. Two in vitro studies reported a positive effect of the chemical chaperone sodium 4-phenylbutyrate (4-PBA) on mutant UMOD maturation. Thus, 4-PBA was suggested as a potential treatment for UAKD. This study evaluated the effects of 4-PBA in two mouse models of UAKD. In contrast to previous in vitro studies, treatment with 4-PBA did not increase HSP70 expression or improve maturation and trafficking of mutant UMOD in vivo. Kidney function of UAKD mice was actually deteriorated by 4-PBA treatment. In transfected tubular epithelial cells, 4-PBA did not improve maturation but increased the expression level of both mutant and wild-type UMOD protein. Activation of NF-κB pathway in thick ascending limb of Henle's loop cells of UAKD mice was detected by increased abundance of RelB and phospho-IκB kinase α/β, an indirect activator of NF-κB. Furthermore, the abundance of NF-κB1 p105/p50, NF-κB2 p100/p52, and TRAF2 was increased in UAKD. NF-κB activation was identified as a novel disease mechanism of UAKD and might be a target for therapeutic intervention.
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