Senescence marker protein 30 protects intestinal epithelial cells against inflammation-induced cell death by enhancing Nrf2 activity

Publication date: December 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Volume 1864, Issue 12Author(s): Jieun Choo, Gwangbeom Heo, Su Jin Kim, Yunna Lee, Akihito Ishigami, Naoki Maruyama, Hae Young Chung, Eunok ImAbstractSenescence marker protein 30 (SMP30) is a calcium-binding protein whose expression decreases during senescence. SMP30 deficiency increases susceptibility to cytokine-induced apoptosis in the liver and to radiation-induced apoptosis in the small intestine. Furthermore, colonic epithelial cell death is associated with the severity of colitis. Therefore, in the present study, we investigated the function of SMP30 during intestinal inflammation. In SMP30 deficient mice, colitis was significantly exacerbated as demonstrated by increased mortality (p = 0.001), body weight loss (p = 0.0105 at day 8), rectal bleeding (p = 0.0047 at day 8) and diarrhea (p = 0.0030 at day 8), histological scores (ulcers, p = 0.0002; edema, p = 0.0125; leukocyte infiltration, p = 0.0016) and productions of pro-inflammatory cytokines (IL-1α, p = 0.0452; IL-6, p = 0.0074; G-CSF, p = 0.0036). In addition, greater proportions of apoptotic cells and lower levels of anti-apoptotic marker proteins (total PARP-1 and Bcl-2) were observed in the inflamed intestines of SMP30 deficient mice than in wild type controls. In vitro experiments on colonic epithelial cells showed that stable SMP30 expression inhibited but that SMP30...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - Category: Molecular Biology Source Type: research