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Cataract is lens opacity, which is a common blinding eye disease worldwide. Aquaporin 5 (AQP5) is expressed in the human and mouse lenses. This study aimed to investigate the underlying mechanisms of AQP5 in the senescence of lens epithelial cells (LECs). Primary LECs were isolated and cultured from Aqp5 +/+ and Aqp5 −/− mice. Western blot or immunofluorescence staining of p16, Ki67, MitoSOX, JC-1 and phalloidin was used in the experiments to evaluate the changes in the primary LECs. The primary Aqp5 −/− LECs showed increased p16 expression and mitochondrial reactive oxygen species, decreased mitochondrial membrane potential and activity, and cytoskeletal disorders. When the cells were pretreated with Mito-TEMPO, the Aqp5 −/− mice showed decreased p16 expression, reduced mitochondrial dysfunction and cytoskeletal disorders. Our results revealed that AQP5 deficiency promotes the senescence of primary LECs through mitochondrial dysfunction. This provides a new perspective for the treatment of cataracts by regulating AQP5 expression. • AQP5 deficiency promotes the senescence of lens epithelial cells. • AQP5 deficiency results in mitochondrial dysfunction in lens epithelial cells. • The involvement of AQP5 in treating age-related cataracts offers a novel therapeutic approach for ocular disorders. [ABSTRACT FROM AUTHOR]

Abstract: The WL5 antibody is an anti-colorectal cancer antibody secreted by the WL5 hybridoma clone. Flow cytometric analysis showed that WL5 specifically binds to the HT29 and LS180 colorectal cancer cell lines. Immunohistochemical analysis performed on a tissue microarray demonstrated that the WL5 antibody can be used for the specific and sensitive diagnosis of colorectal carcinoma. Furthermore, WL5 mediated antibody dependent cell-mediated cytotoxicity (ADCC) of tumor cells and exhibited similar antitumor activity to adriamycin (ADM) but avoided the cardiomyopathy and decrease in peripheral white blood cell counts associated with prolonged ADM treatment. The glycoprotein, carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), was identified as the target antigen of WL5 through immunoprecipitation and mass spectrometric analyses, which might provide a potential biomarker and therapeutic target for colorectal cancer. [Copyright &y& Elsevier]

Abstract: Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is a member of the immunoglobulin super family and has been observed to have two paradoxical functions: tumor suppression and the promotion of tumor invasion. In the present study, we discovered that CEACAM1 functions as an adhesion inhibitor and a migration promoter. The CEACAM1 transfected cells, either 293-CEACAM1 or LOVO/trans-CEACAM1, was proved to have lower adhesion rate. Furthermore, HT29/siRNA-CEACAM1 cells had a higher adhesion rate than HT29 cells. These results indicated that CEACAM1 was an inhibitor of cell-matrix adhesion. Additionally, 293-CEACAM1 LOVO/trans-CEACAM1 cells exhibited better motility in a trans-well migration assay. N-cadherin expression levels were positively correlated with CEACAM1 in 293-CEACAM1, LOVO/trans-CEACAM1 and HT29/siRNA-CEACAM1 cells. When blocked by a GC-4 antibody, the adhesive capacities of 293-CEACAM1 and LOVO/trans-CEACAM1 were recovered and the motilities of them were suppressed, which suggested that CEACAM1 functioned through N-cadherin. [Copyright &y& Elsevier]

Annexin A1 (AnxA1) has been shown to exert potent anti-inflammatory and anti-fibrotic activities in a range of systemic inflammatory disorders. Corneal scarring is characterized by myofibroblast differentiation and disorganized extracellular matrix deposition. This study was aim to explore the potential therapeutic properties of Ac2-26, a mimetic peptide of AnnexinA1 (AnxA1), on TGF-β induced human corneal myofibroblast differentiation and mechanical injury-induced mouse corneal haze. The results found that Ac2-26 treatment dose dependently reduced α-SMA level and other fibrogenic gene expressions in HTK cells stimulated by exogenous TGF-β1. While this anti-fibrotic effect was abolished by an FPR2/ALX inhibitor WRW4. In mice, topical Ac2-26 application suppressed the development of corneal scarring, inhibited myofibroblast differentiation, while promoted the corneal epithelial wound healing. Moreover, Ac2-26 treatment inhibited Ly6G + neutrophil infiltration and reduced corneal inflammatory response. The results provided in vivo and in vitro supports the anti-fibrotic and anti-inflammatory effects of AnxA1 derived peptide Ac2-26, and suggest that AnxA1 mimetic agents might be a promising strategy for the treatment of corneal scarring. • Ac2-26 inhibits myofibroblast differentiation in HTK cells via FPR2. • Topical Ac2-26 attenuated corneal scarring formation and inflammatory response in vivo. • AnxA1 mimetic agents might be a promising strategy for the treatment of corneal fibrosis. [ABSTRACT FROM AUTHOR]