title: Heat shock protein Gp96 as potential regulator of morphostasis after partial hepatectomy in mice.
abstract: Gp96 (also known as glucose-regulated protein 94, endoplasmin) is the endoplasmic reticulum (ER)-resident protein, which belongs to the heat shock protein HSP90 family. It is upregulated in response to glucose starvation and other stressful stimuli that disrupt protein synthesis in the ER. There, it is acting as a molecular chaperon involved in the correction of unfolded proteins, in the activation of proteasome-dependent ER-associated degradation of the misfolded proteins, and in activation of protein translations that modulate the polypeptide traffic into the ER. In addition, it has been implicated in antigen presentation and MHC class I and II upregulation, in the activation and maturation of dendritic cells and proinflammatory cytokine secretion, as well as in chaperoning of integrins and Toll-like receptors, acting as a "danger signal" to the innate and adaptive immunity. Moreover, owing to its specific function in Ca2+ homeostasis and in the insulin- IGF/signaling pathways, it has been proposed that gp96 might participate in mechanisms that are critical for cell growth, differentiation, and responses to ER stress. Emphasizing that gp96, as a natural adjuvant for chaperoning antigenic self peptides into the immune surveillance pathways, may also be involved in the maintenance of morphostasis and self tolerance, in this survey we show that high levels of upregulation of gp96 in regenerating liver and thymus are followed by signs of transient autoimmunity, augmented apoptosis in thymus, and the presence of autoreactive NKT and regulatory T cells that might be involved in the control of rapid liver growth induced by partial hepatectomy.
authors: Department of Physiology and Immunology, Medical School, University of Rijeka, Rijeka, Croatia. biserr@medri.uniri.hr
authors: Biserka
authors: B
authors: Radosevic-Stasic
authors: Hrvoje
authors: H
authors: Jakovac
authors: Damir
authors: D
authors: Grebic
authors: Zlatko
authors: Z
authors: Trobonjaca
authors: Ines
authors: I
authors: Mrakovcic-Sutic
authors: Mira
authors: M
authors: Cuk
mesh_terms: D000818:Animals; D017209:Apoptosis; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D006498:Hepatectomy; D008099:Liver / Q000276:immunology / Q000378:metabolism* / Q000601:surgery*; D008115:Liver Regeneration; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D055611:Natural Killer T-Cells / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction; D013154:Spleen / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism; D013950:Thymus Gland / Q000276:immunology / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D008562:Membrane Glycoproteins; C053387:endoplasmin