Hepatic stellate cells (vitamin A-storing cells) change their cytoskeleton structure by extracellular matrix components through a signal transduction system.
When cultured on a polystyrene surface or aminoalkylsilane-coated cover glasses, rat and human hepatic stellate cells exhibit a flattened, fibroblast-like shape with well-developed stress fibers. However, culturing the cells on type I collagen gel results in the elongation of long, multipolar cellular processes, whereas cells cultured on Matrigel maintain their round shapes. Dual fluorescence staining of microtubules and fibrillar actin indicated that the processes extend together with collagen fibers and contained microtubules as the core, whereas the periphery contained fibrillar actin. Immunofluorescence staining of vinculin showed that the focal adhesions were distributed mainly in lamellipodia when cultured on aminoalkylsilane-coated cover glasses, whereas in the cells cultured on type I collagen gel they were localized to the tips of the processes and along their bottom surface contacting collagen fibers. Wortmannin, as well as staurosporin and herbimycin A, inhibited the elongation process and induced the retraction of elongated processes. The wortmannin treatment also resulted in an alteration in focal adhesion distribution from the processes to cell bodies. These results indicate that the cell surface integrin binding to interstitial collagen fibers induces the elongation of processes through signaling events and the subsequent cytoskeleton assembly in hepatic stellate cells.
Department of Anatomy, Akita University School of Medicine, Japan.
N
N
Kojima
M
M
Sato
K
K
Imai
M
M
Miura
Y
Y
Matano
H
H
Senoo
D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D016227:Benzoquinones; D048429:Cell Size; D003094:Collagen / Q000494:pharmacology; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D047029:Lactams, Macrocyclic; D008099:Liver / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D019000:Phosphotyrosine / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011809:Quinones / Q000494:pharmacology; D051381:Rats; D017828:Rifabutin / Q000031:analogs & derivatives; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D019311:Staurosporine / Q000494:pharmacology; D016608:Talin / Q000378:metabolism; D014407:Tumor Cells, Cultured; D016596:Vinculin / Q000378:metabolism; D014801:Vitamin A / Q000378:metabolism*; D000077191:Wortmannin
D000730:Androstadienes; D016227:Benzoquinones; D004791:Enzyme Inhibitors; D016326:Extracellular Matrix Proteins; D047029:Lactams, Macrocyclic; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011809:Quinones; D016608:Talin; D014801:Vitamin A; D016596:Vinculin; D017828:Rifabutin; D019000:Phosphotyrosine; C020754:herbimycin; D003094:Collagen; D011505:Protein-Tyrosine Kinases; D019311:Staurosporine; D000077191:Wortmannin