Anti-TMEM119 (aa 194-282) polyclonal antibody

The objective of this study is to characterize the retinal degeneration (RD) phenotype of CXCR5/NRF2 double knockout (DKO) mice at the early adult age. CXCR5 KO mice and NRF2 KO mice were bred to create CXCR5/NRF2 DKO mice. The assessment of RD features included fundus and optical coherence tomography (OCT) imaging, periodic acid-Schiff (PAS), and immunofluorescence staining of retinal pigment epithelium (RPE)-choroid flat-mounts. Stained samples were imaged with fluorescent microscopy, and Western blots were used to monitor protein expression changes. The staining of cleaved caspase-3 and PNA-lectin was performed to assess the presence of photoreceptor cell apoptosis. Quantification and statistical analyses were performed with Image J and Graphpad software. The young adult (2-6 months) DKO mice exhibited increased hypopigmented spots on fundus and subRPE abnormalities on OCT as compared to the CXCR5-KO mice, and C57BL6 WT controls. PAS-stained sections demonstrated aberrant RPE/sub-RPE depositions. The DKO mice had increased sub-RPE depositions of IgG and AMD-associated proteins (beta-amyloid, Apolipoprotein-E, C5b-9, and alpha B-crystallin). The protein expression of AMD-associated proteins and microglia marker (TMEM119) were upregulated at the RPE/BM/choroid complex of DKO mice. The adult DKO mice underwent photoreceptor cell apoptosis compared to the single CXCR5 and NRF2 KO and the WT mice at an early adult age. Mechanistically increased expression of CXCL13 and N-cadherin was observed as a sign of epithelial-mesenchymal transition. The data suggest that the CXCR5/NRF2-DKO mice develop RD characteristics at an early age and may serve as a valuable animal model of RD.

Gastric cancer is the second major cause of death associated with cancer and ranks among the top four cancers diagnosed worldwide. Previous findings identified the association of transmembrane proteins (TMEMs) with tumorigenesis of various types of cancer, including breast, liver and kidney cancer. However, the expression and the biological function of TMEMs, especially TMEM119, and its possible molecular mechanism in gastric cancer remain less understood. CCK-8 and flow cytometric analysis was employed to examine the viability and apoptosis of gastric adenocarcinoma SGC-7901 and AGS cells, gastric carcinoma MKN45 cells, as well as gastric epithelial cell lines GES-1 after transfection with TMEM119-siRNA (siTMEM119), respectively. Quantitative PCR, western blot analysis and immunohistochemistry was performed to detect the expression levels of TMEM119, Bax, Bcl-2 and caspase-3. The results showed that, TMEM119 was elevated with the highest expression detected in SGC-7901 cells compared to AGS cells, MKN45 cells, as well as GES-1. TMEM119 silencing in the gastric cancer cell line, SGC-7901, significantly inhibited cell viability and induced apoptosis. The downregulation of TMEM119 exhibited reduced levels of Bcl-2 and higher levels of Bax and caspase-3 in SGC-7901 cells. These results suggest that TMEM119 is useful in the treatment of gastric cancer.