Ubiquitin-fold modifier 1 inhibits apoptosis by suppressing the endoplasmic reticulum stress response in Raw264.7...

Ubiquitin-fold modifier 1 (Ufm1) is a new member of the ubiquitin-like protein family, and its biological function remains largely unknown, particularly in macrophages. In this study, we demonstrate that Ufm1 expression is increased in diabetic mouse resident peritoneal macrophages (RPMs) and in the mouse macrophage cell line, Raw264.7, subjected to endoplasmic reticulum (ER) stress. Following treatment of the cells with the ER stress inducers, thapsigargin (TG) or tunicamycin (TM), the lentiviral short hairpin RNA (shRNA)-mediated knockdown of Ufm1 increased the apoptosis of Raw264.7 cells. Furthermore, these cells had higher expression levels of immunoglobulin heavy chain-binding protein (BiP) and C/EBP homologous protein (CHOP), which are markers of the ER stress response. The overexpression of Ufm1 induced by lentiviral infection in the Raw264.7 cells treated with the ER stress inducers, TG or TM, resulted in the opposite effect. Taken together, our results suggest that Ufm1 is upregulated in diabetic mouse RPMs and in Raw264.7 cells in response to ER stress and that Ufm1 protects macrophages against apoptosis. Thus, Ufm1 may be a novel gene that protects against ER stress-induced apoptosis in macrophages.