ArticleBMC developmental biology2015
Hsp90 and hepatobiliary transformation during sea lamprey metamorphosis.
Article in BMC developmental biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 8 citations in OpenAlex.
- The ProbioticAnimals : an open access journal from MDPI · 2023Article
- Biliary Atresia Animal Models: Is the Needle in a Haystack?International journal of molecular sciences · 2022Review
- The Disassociation of the A20/HSP90 ComplexFrontiers in oncology · 2021Article
- Recent developments in etiology and disease modeling of biliary atresia: a narrative review.Digestive medicine research · 2020Article
- TGF-β Signaling Plays a Pivotal Role During Developmental Biliary Atresia in Sea Lamprey (Hepatology communications · 2020Article
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundBiliary atresia (BA) is a human infant disease with inflammatory fibrous obstructions in the bile ducts and is the most common cause for pediatric liver transplantation. In contrast, the sea lamprey undergoes developmental BA with transient cholestasis and fibrosis during metamorphosis, but emerges as a fecund adult. Therefore, sea lamprey liver metamorphosis may serve as an etiological model for human BA and provide pivotal information for hepatobiliary transformation and possible therapeutics.
resultsWe hypothesized that liver metamorphosis in sea lamprey is due to transcriptional reprogramming that dictates cellular remodeling during metamorphosis. We determined global gene expressions in liver at several metamorphic landmark stages by integrating mRNA-Seq and gene ontology analyses, and validated the results with real-time quantitative PCR, histological and immunohistochemical staining. These analyses revealed that gene expressions of protein folding chaperones, membrane transporters and extracellular matrices were altered and shifted during liver metamorphosis. HSP90, important in protein folding and invertebrate metamorphosis, was identified as a candidate key factor during liver metamorphosis in sea lamprey. Blocking HSP90 with geldanamycin facilitated liver metamorphosis and decreased the gene expressions of the rate limiting enzyme for cholesterol biosynthesis, HMGCoA reductase (hmgcr), and bile acid biosynthesis, cyp7a1. Injection of hsp90 siRNA for 4 days altered gene expressions of met, hmgcr, cyp27a1, and slc10a1. Bile acid concentrations were increased while bile duct and gall bladder degeneration was facilitated and synchronized after hsp90 siRNA injection.
conclusionsHSP90 appears to play crucial roles in hepatobiliary transformation during sea lamprey metamorphosis. Sea lamprey is a useful animal model to study postembryonic development and mechanisms for hsp90-induced hepatobiliary transformation.
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