title: Modulation of the expression of connective tissue growth factor by alterations of the cytoskeleton.
abstract: Modulation of the cytoskeletal architecture was shown to regulate the expression of CTGF (connective tissue growth factor, CCN2). The microtubule disrupting agents nocodazole and colchicine strongly up-regulated CTGF expression, which was prevented upon stabilization of the microtubules by paclitaxel. As a consequence of microtubule disruption, RhoA was activated and the actin stress fibers were stabilized. Both effects were related to CTGF induction. Overexpression of constitutively active RhoA induced CTGF synthesis. Interference with RhoA signaling by simvastatin, toxinB, C3 toxin, and Y27632 prevented up-regulation of CTGF. Likewise, direct disintegration of the actin cytoskeleton by latrunculin B interfered with nocodazole-mediated up-regulation of CTGF expression. Disassembly of actin fibers by cytochalasin D, however, unexpectedly increased CTGF expression indicating that the content of F-actin per se was not the major determinant for CTGF gene expression. Given the fact that cytochalasin D sequesters G-actin, a decrease in G-actin increased CTGF, while increased levels of G-actin corresponded to reduced CTGF expression. These data link alterations in the microtubule and actin cytoskeleton to the expression of CTGF and provide a molecular basis for the observation that CTGF is up-regulated in cells exposed to mechanical stress.
authors.affiliation: Medizinische Klinik IV, Universität Erlangen-Nürnberg, Loschgestrasse 8, D-91054 Erlangen, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Ott
authors.forename: Dominika
authors.initials: D
authors.lastname: Iwanciw
authors.forename: Angela
authors.initials: A
authors.lastname: Graness
authors.forename: Klaudia
authors.initials: K
authors.lastname: Giehl
authors.forename: Margarete
authors.initials: M
authors.lastname: Goppelt-Struebe
mesh_terms: D000199:Actins / Q000032:analysis; D000577:Amides / Q000494:pharmacology; D001426:Bacterial Proteins; D001427:Bacterial Toxins / Q000494:pharmacology; D001905:Botulinum Toxins / Q000494:pharmacology; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D002461:Cell Line, Transformed; D003078:Colchicine / Q000494:pharmacology; D055513:Connective Tissue Growth Factor; D015638:Cytochalasin D / Q000494:pharmacology; D003599:Cytoskeleton / Q000737:chemistry / Q000187:drug effects / Q000648:ultrastructure*; D005347:Fibroblasts; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D007668:Kidney; D015739:Nocodazole / Q000494:pharmacology; D017239:Paclitaxel / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D019821:Simvastatin / Q000494:pharmacology; D013314:Stress, Mechanical; D013844:Thiazoles / Q000494:pharmacology; D053778:Thiazolidines; D020742:rhoA GTP-Binding Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D000199:Actins; D000577:Amides; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D019086:Bridged Bicyclo Compounds, Heterocyclic; C526317:CCN2 protein, human; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D011725:Pyridines; D013844:Thiazoles; D053778:Thiazolidines; C031815:toxB protein, Clostridium difficile; C108830:Y 27632; D055513:Connective Tissue Growth Factor; D015638:Cytochalasin D; D019821:Simvastatin; D001905:Botulinum Toxins; D020742:rhoA GTP-Binding Protein; C096324:botulinum toxin type C; C037068:latrunculin B; D017239:Paclitaxel; D015739:Nocodazole; D003078:Colchicine