Naslov
Heat shock protein gp96 as potential regulator of morphostasis after partial hepatectomy in mice

Autori
Radošević-Stašić, Biserka ; Jakovac, Hrvoje ; Grebić, Damir ; Trobonjača, Zlatko ; Mrakovčić-Šutić, Ines ; Ćuk, Mira

Izvornik
Current aging science (1874-6098) 5 (2012), 3; 254-262

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, pregledni rad, znanstveni

Ključne riječi
heat shock protein-gp96; liver regeneration; NK cells; NKT cells; partial hepatectomy; regulatory T cells; self-antigens; tolerance.

Sažetak
Gp96 (known also 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 translation 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 was proposed that gp96 might participate in mechanisms that are critical for cell growth, differentiation and responses to ER stress. Underlining that gp96, as a natural adjuvant for chaperoning antigenic self peptides into the immune surveillance pathways, may be also involved in the maintenance of morphostasis and self tolerance, in this survey we show that high upregulation of gp96 in regenerating liver and thymus is followed by signs of transient autoimmunity, augmented apoptosis in thymus and presence of autoreactive NKT and regulatory T cells that might be involved in the control of fast liver growth induced by partial hepatectomy.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA