Translocation of p21 Cip1/WAF1 from the nucleus to the cytoplasm correlates with pancreatic myofibroblast to fibroblast cell conversion

Manapov, F.; Muller, P.; Rychly, J.
June 2005
Gut;Jun2005, Vol. 54 Issue 6, p814
Academic Journal
Background and aims: In the pancreas, myofibroblasts (MFBs) were shown to play an important role in the cellular response during inflammation and injury. However, there is only fragmentary information concerning the fate of these cells in pancreas regeneration and fibrosis development. Methods: Explant cultures of rat pancreatic tissue were used as a model to follow cellular dynamics and phenotype conversion of pancreatic MESs in vitro. For detailed biochemical analyses a pancreatic fibroblast cell line (long culture fibroblast (LCF)) was generated from MESs in a long term culture. Cerulein induced acute pancreatitis and dibutyltin dichloride induced pancreas fibrosis were used as experimental models for acute and chronic fibrogenic reactions, respectively. Results: In the explant culture, pancreatic MESs which derived from fat storing fibroblastic cells underwent apoptosis or converted again to fibroblasts. The phenotype switch to fibroblasts was associated with translocation of p21Cip1/WAF1 from the nucleus into the cytoplasm. Molecular analyses in LCFs revealed subsequent binding to and inhibition of the activities of Rho kinase 2 and apoptosis signal regulating kinase 1. In the experimentally established pancreas fibrosis, fibroblasts with cytoplasmic expression of were distributed throughout fibrotic bands whereas in experimental acute pancreatitis MFBs with nuclear expression of Cip1/WAF1 dominated. Conclusions: The results indicate that pancreatic MFBs are transient and suggest that intracellular localisation of Cip1/WAF1 can contribute to the phenotype conversion of these cells to fibroblasts in culture and experimental injury.


Related Articles

  • Baseline levels of chromosome instability in the human lymphoblastoid cell TK6. Jeffrey L. Schwartz; Robert Jordan; Helen H. Evans; Marek Lenarczyk; Howard L. Liber // Mutagenesis;Nov2004, Vol. 19 Issue 6, p477 

    Induced genomic instability in the human B lymphoblastoid cell line TK6 manifests itself as increases in end-to-end chromosome fusions and non-reciprocal chromosome translocations. It is not associated with elevated frequencies of specific locus mutations or other cytogenetic alterations....

  • Three-dimensional analysis of DNA replication foci: a comparative study on species and cell type in situ. Cossmann, Peter H.; Eggli, Peter S.; Kurz, Haymo // Histochemistry & Cell Biology;Mar2000, Vol. 113 Issue 3, p195 

    Chromatin morphology of interphase nuclei in most cell lines of quail (Coturnix coturnix japonica) and chick (Gallus gallus domesticus) embryos shows typical interspecies differences. This intrinsic marker has been used in quail/chick chimerisation experiments, where also differences between...

  • Generation of Recombinant Chinese Hamster Ovary Cell Lines by Microinjection. Derouazi, Madiha; Flaction, Rachel; Girard, Philippe; de Jesus, Maria; Jordan, Martin; Wurm, Florian M. // Biotechnology Letters;Mar2006, Vol. 28 Issue 6, p373 

    Microinjection is a gene transfer technique enabling partial control of plasmid delivery into the nucleus or cytoplasm of cultured animal cells. Here this method was used to establish various recombinant mammalian cell lines. The injection volume was estimated by fluorescence quantification of...

  • In Vitro Host-Cell Susceptibility to Usutu Virus. Bakonyi, Tamás; Lussy, Helga; Weissenböck, Herbert; Hornyák, Ákos; Nowotny, Norbert // Emerging Infectious Diseases;Feb2005, Vol. 11 Issue 2, p298 

    We investigated the susceptibility to Usutu virus (Flavivirus) of 13 permanent cell lines, 3 primary cell cultures, and chicken embryos. Vero, PK-15, and goose embryo fibroblast cells developed cytopathic effects; however, viral multiplication was detected in all mammalian cell types by...

  • Comparative analysis of the nucleosome structure of cell nuclei by small-angle neutron scattering. Isaev-Ivanov, V. V.; Lebedev, D. V.; Lauter, H.; Pantina, R. A.; Kuklin, A. I.; Islamov, A. Kh.; Filatov, M. V. // Physics of the Solid State;May2010, Vol. 52 Issue 5, p1063 

    The nucleosome structure in native nuclei of normal (chicken erythrocyte and rat leukocyte nuclei) and anomalously proliferating (the human cervical adenocarcinoma cell line HeLa and the Chinese hamster fibroblast cell line A238) cells has been investigated using small-angle neutron scattering....

  • Immunolocalization of NuMA and phosphorylated proteins during the cell cycle in human breast and prostate cancer cells as analyzed by immunofluorescence and postembedding immunoelectron microscopy. Gobert, Geoffrey N.; Hueser, Christopher N.; Curran, Edward M.; Sun, Qing-Yuan; Glinsky, Vladislav V.; Welshons, Wade V.; Eisenstark, Abraham; Schatten, Heide // Histochemistry & Cell Biology;May2001, Vol. 115 Issue 5, p381 

    The formation of mitotic centrosomes is a complex process in which a number of cellular proteins translocate to mitotic poles and play a critical role in the organization of the mitotic apparatus. The 238-kDa nuclear mitotic apparatus protein NuMA is one of the important proteins that plays a...

  • Intracellular localization of regulatory proteins of the German cockroach Blattella germanica densovirus. Martynova, E.; Kapelinskaya, T.; Schal, C.; Mukha, D. // Molecular Biology;Mar2014, Vol. 48 Issue 2, p301 

    The use of western blot analysis of nuclear and cytoplasmic extracts of BgDNV densovirusinfected German cockroach, Blattella germanica, the intracellular localization of the regulatory proteins of the corresponding densovirus was investigated in cell culture. It was demonstrated that two...

  • Candidate Causal Regulatory Effects by Integration of Expression QTLs with Complex Trait Genetic Associations. Nica, Alexandra C.; Montgomery, Stephen B.; Dimas, Antigone S.; Stranger, Barbara E.; Beazley, Claude; Barroso, Inês; Dermitzakis, Emmanouil T. // PLoS Genetics;Apr2010, Vol. 6 Issue 4, p1 

    The recent success of genome-wide association studies (GWAS) is now followed by the challenge to determine how the reported susceptibility variants mediate complex traits and diseases. Expression quantitative trait loci (eQTLs) have been implicated in disease associations through overlaps...

  • Tetrapeptide H-Ala-Glu-Asp-Arg-OH Stimulates Expression of Cytoskeletal and Nuclear Matrix Proteins. Khavinson, V.; Lin'kova, N.; Polyakova, V.; Kvetnoy, I.; Benberin, V.; D'yakonov, M.; Titkov, Yu. // Bulletin of Experimental Biology & Medicine;Aug2012, Vol. 153 Issue 4, p559 

    Tetrapeptide H-Ala-Glu-Asp-Arg-OH enhances the expression of cytoskeletal (actin, tubulin, vimentin) and nuclear matrix proteins (lamin A, lamin C) in cultured mouse embryonic fibroblasts by 2-5 and 2-3 times, respectively. Thus, the previously reported cardioprotective activity of this...


Read the Article


Sign out of this library

Other Topics