ArticlePloS one2013
Tacrolimus (FK506) prevents early stages of ethanol induced hepatic fibrosis by targeting LARP6 dependent mechanism of collagen synthesis.
Article in PloS one, 2013. 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 16 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
16 citing papers in PubMed, 25 citations in OpenAlex.
- Nickel-Catalyzed Cross-Dehydrogenative Coupling of Aldehydes and Alkenes toward Skipped Enones.Journal of the American Chemical Society · 2025Article
- Article
- Effect of mycophenolate mofetil alleviates carbon tetrachloride-induced liver fibrosis in mice.Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2023Article
- Discovery of a Lead Compound for Specific Inhibition of Type I Collagen Production in Fibrosis.ACS medicinal chemistry letters · 2021Article
- Roles of glycogen synthase kinase 3 alpha and calcineurin in regulating the ability of sperm to fertilize eggs.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Expression of hepatic stellate cell activation-related genes in HBV-, HCV-, and nonalcoholic fatty liver disease-associated fibrosis.PloS one · 2020Article
- Co-administration of everolimus and N-acetylcysteine attenuates hepatic stellate cell activation and hepatic fibrosis.American journal of translational research · 2020Article
- Intestinal stenosis in Crohn's disease shows a generalized upregulation of genes involved in collagen metabolism and recognition that could serve as novel anti-fibrotic drug targets.Therapeutic advances in gastroenterology · 2020Article
- Discovery and evaluation of inhibitor of LARP6 as specific antifibrotic compound.Scientific reports · 2019Article
- Article
- Article
- LARP6 Meets Collagen mRNA: Specific Regulation of Type I Collagen Expression.International journal of molecular sciences · 2016Review
- Akt mediated phosphorylation of LARP6; critical step in biosynthesis of type I collagen.Scientific reports · 2016Article
- Insulin-like growth factor-1 increases synthesis of collagen type I via induction of the mRNA-binding protein LARP6 expression and binding to the 5' stem-loop of COL1a1 and COL1a2 mRNA.The Journal of biological chemistry · 2014Article
- Role of LARP6 and nonmuscle myosin in partitioning of collagen mRNAs to the ER membrane.PloS one · 2014Article
- Characterization of binding of LARP6 to the 5' stem-loop of collagen mRNAs: implications for synthesis of type I collagen.RNA biology · 2014Article
Corrections and comments
- Erratum issued
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Tacrolimus (FK506) is a widely used immunosuppressive drug. Its effects on hepatic fibrosis have been controversial and attributed to immunosuppression. We show that in vitro FK506, inhibited synthesis of type I collagen polypeptides, without affecting expression of collagen mRNAs. In vivo, administration of FK506 at a dose of 4 mg/kg completely prevented development of alcohol/carbon tetrachloride induced liver fibrosis in rats. Activation of hepatic stellate cells (HSCs) was absent in the FK506 treated livers and expression of collagen α2(I) mRNA was at normal levels. Collagen α1(I) mRNA was increased in the FK506 treated livers, but this mRNA was not translated into α1(I) polypeptide. No significant inflammation was associated with the fibrosis model used. FK506 binding protein 3 (FKBP3) is one of cellular proteins which binds FK506 with high affinity. We discovered that FKBP3 interacts with LARP6 and LARP6 is the major regulator of translation and stability of collagen mRNAs. In the presence of FK506 the interaction between FKBP3 and LARP6 is weakened and so is the pull down of collagen mRNAs with FKBP3. We postulate that FK506 inactivates FKBP3 and that lack of interaction of LARP6 and FKBP3 results in aberrant translation of collagen mRNAs and prevention of fibrosis. This is the first report of such activity of FK506 and may renew the interest in using this drug to alleviate hepatic fibrosis.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.