Molecular basis for calcium signaling in hepatic stellate cells
| Autor: | Emma A. Kruglov, Jin Yu, Jonathan A. Dranoff, Gaurav Arora, Paulo Renato A.V. Correa, Michael H. Nathanson |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Liver Cirrhosis
Male Pathology medicine.medical_specialty Time Factors Cirrhosis Physiology Liver cytology Active Transport Cell Nucleus Nucleoplasmic reticulum chemistry.chemical_element Calcium Biology Endoplasmic Reticulum Rats Sprague-Dawley Adenosine Triphosphate Physiology (medical) medicine Animals Inositol 1 4 5-Trisphosphate Receptors Calcium Signaling RNA Messenger Cell Shape Cells Cultured Calcium signaling Cell Nucleus Microscopy Confocal Microscopy Video Hepatology Receptors Purinergic P2 Gastroenterology medicine.disease Rats Liver chemistry Hepatic stellate cell Cell Surface Extensions Signal transduction Calreticulin Hepatic fibrosis |
| Zdroj: | American Journal of Physiology-Gastrointestinal and Liver Physiology. 292:G975-G982 |
| ISSN: | 1522-1547 0193-1857 |
| Popis: | Progressive liver fibrosis (with the resultant cirrhosis) is the primary cause of chronic liver failure. Hepatic stellate cells (HSCs) are critically important mediators of liver fibrosis. In the healthy liver, HSCs are quiescent lipid-storing cells limited to the perisinusoidal endothelium. However, in the injured liver, HSCs undergo myofibroblastic transdifferentiation (activation), which is a critical step in the development of organ fibrosis. HSCs express P2Y receptors linking extracellular ATP to inositol (1,4,5)-trisphosphate-mediated cytosolic Ca2+ signals. Here, we report that HSCs express only the type I inositol (1,4,5)-trisphosphate receptor and that the receptor shifts into the nucleus and cell extensions upon activation. These cell extensions, furthermore, express sufficient machinery to enable local application of ATP to evoke highly localized Ca2+ signals that induce localized contractions. These autonomous units of subcellular signaling and response reveal a new level of subcellular organization, which, in turn, establishes a novel paradigm for the local control of fibrogenesis in the liver. |
| Databáze: | OpenAIRE |
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