Evidence map›Paper›PMID 11487529›Full record

ArticleBritish journal of pharmacology2001

Rho-dependent inhibition of the induction of connective tissue growth factor (CTGF) by HMG CoA reductase inhibitors (statins).

M Eberlein, J Heusinger-Ribeiro, M Goppelt-Struebe

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PubMed Full text at PMC Publisher
In one paragraph

Article in British journal of pharmacology, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed, 1 pooled it
3.0field-weighted citation impact, top 8% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

31 citing papers in PubMed, 1 synthesis or guideline pooled it, 130 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors at 1 institution in 1 country.

M EberleinMedizinische Klinik IV, Universität Erlangen-Nürnberg, Loschgestrasse 8, D-91054 Erlangen, Germany.
J Heusinger-Ribeiro
M Goppelt-Struebe
Friedrich-Alexander-Universität Erlangen-Nürnberg · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

It was supposed that inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG CoA) reductase (statins) might inhibit the expression of the fibrosis-related factor CTGF (connective tissue growth factor) by interfering with the isoprenylation of Rho proteins. The human renal fibroblast cell line TK173 was used as an in vitro model system to study the statin-mediated modulation of the structure of the actin cytoskeleton and of the expression of CTGF mRNA. Incubation of the cells with simvastatin or lovastatin time-dependently and reversibly changed cell morphology and the actin cytoskeleton with maximal effects observed after about 18 h. Within the same time period, statins reduced the basal expression of CTGF and interfered with CTGF induction by lysophosphatidic acid (LPA) or transforming growth factor beta. Simvastatin and lovastatin proved to be much more potent than pravastatin (IC(50) 1 - 3 microM compared to 500 microM). The inhibition of CTGF expression was prevented when the cells were incubated with mevalonate or geranylgeranylpyrophosphate (GGPP) but not by farnesylpyrophosphate (FPP). Specific inhibition of geranylgeranyltransferase-I by GTI-286 inhibited LPA-mediated CTGF expression whereas an inhibitor of farnesyltransferases FTI-276 was ineffective. Simvastatin reduced the binding of the small GTPase RhoA to cellular membranes. The effect was prevented by mevalonate and GGPP, but not FPP. These data are in agreement with the hypothesis that interference of statins with the expression of CTGF mRNA is primarily due to interference with the isoprenylation of RhoA, in line with previous studies, which have shown that RhoA is an essential mediator of CTGF induction. The direct interference of statins with the synthesis of CTGF, a protein functionally related to the development of fibrosis, may thus be a novel mechanism underlying the beneficial effects of statins observed in renal diseases.

Indexed as

Intercellular Signaling Peptides and ProteinsActinsBlotting, NorthernCell LineConnective Tissue Growth FactorCytoskeletonDose-Response Relationship, DrugGene Expression RegulationGrowth SubstancesHumansHydroxymethylglutaryl-CoA Reductase InhibitorsImmediate-Early ProteinsLovastatinLysophospholipidsMevalonic AcidPolyisoprenyl PhosphatesActinsCCN2 protein, humanConnective Tissue Growth Factorfarnesyl pyrophosphategeranylgeranyl pyrophosphateGrowth SubstancesHydroxymethylglutaryl-CoA Reductase InhibitorsImmediate-Early ProteinsIntercellular Signaling Peptides and ProteinsLovastatinLysophospholipidsMevalonic AcidPolyisoprenyl PhosphatesPravastatinrhoA GTP-Binding Proteinrho GTP-Binding ProteinsRNA, MessengerSesquiterpenesSimvastatin

Identifiers

PMID11487529
PMCPMC1572879
OpenAlexW2004456664

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.