Human salivary peptide histatin-1 stimulates epithelial and endothelial cell adhesion and barrier function [Research]
Histatins are multifunctional histidine-rich peptides secreted by the salivary glands and exclusively present in the saliva of higher primates, where they play a fundamental role in the protection of the oral cavity. Our previously published results demonstrated that histatin-1 (Hst1) promotes cell–substrate adhesion in various cell types and hinted that it could also be involved in cell–cell adhesion, a process of fundamental importance to epithelial and endothelial barriers. Here we explore the effects of Hst1 on cellular barrier function. We show that Hst1 improved endothelial barrier integrity, decreased it...
Source: FASEB Journal - August 31, 2017 Category: Biology Authors: van Dijk, I. A., Ferrando, M. L., van der Wijk, A.-E., Hoebe, R. A., Nazmi, K., de Jonge, W. J., Krawczyk, P. M., Bolscher, J. G. M., Veerman, E. C. I., Stap, J. Tags: Research Source Type: research
Assessing the satisfaction and burden within an academic animal care and use program [Research]
Although animal research requires adherence to various regulations and standards, the manner in which compliance is maintained and the degree of additional constraints varies between institutions. Regulatory burden, particularly if institutionally imposed, has become a concern for institutions as increased regulatory expectations result in decreased resources available for research efforts. Faculty, research staff, and support staff engaged in animal research were surveyed to determine what institutional animal care and use committee (IACUC) processes were considered burdensome, the perceived value of some suggested modifi...
Source: FASEB Journal - August 31, 2017 Category: Biology Authors: Norton, J. N., Reynolds, R. P., Chan, C., Valdivia, R. H., Staats, H. F. Tags: Research Source Type: research
The ratio of dihomo-{gamma}-linolenic acid to deoxycholic acid species is a potential biomarker for the metabolic abnormalities in obesity [Research]
Bile acid (BA) signaling regulates fatty acid metabolism. BA dysregulation plays an important role in the development of metabolic disease. However, BAs in relation to fatty acids have not been fully investigated in obesity-related metabolic disorders. A targeted metabolomic measurement of serum BA and free fatty acid profiles was applied to sera of 381 individuals in 2 independent studies. The results showed that the ratio of dihomo--linolenic acid (DGLA) to deoxycholic acid (DCA) species (DCAS) was significantly increased in obese individuals with type 2 diabetes (T2DM) from a case–control study and decreased in th...
Source: FASEB Journal - August 31, 2017 Category: Biology Authors: Lei, S., Huang, F., Zhao, A., Chen, T., Chen, W., Xie, G., Zheng, X., Zhang, Y., Yu, H., Zhang, P., Rajani, C., Bao, Y., Jia, W., Jia, W. Tags: Research Source Type: research
Receptor for advanced glycation end products is targeted by FBXO10 for ubiquitination and degradation [Research]
The receptor for advanced glycation end products (RAGE) is a highly expressed cell membrane receptor serving to anchor lung epithelia to matrix components, and it also amplifies inflammatory signaling during acute lung injury. However, mechanisms that regulate its protein concentrations in cells remain largely unknown. Here we show that RAGE exhibits an extended life span in lung epithelia (t1/2 6 h), is monoubiquitinated at K374, and is degraded in lysosomes. The RAGE ligand ODN2006, a synthetic oligodeoxynucleotide resembling pathogenic hypomethylated CpG DNA, promotes rapid lysosomal RAGE degradation through activation ...
Source: FASEB Journal - August 31, 2017 Category: Biology Authors: Evankovich, J., Lear, T., Mckelvey, A., Dunn, S., Londino, J., Liu, Y., Chen, B. B., Mallampalli, R. K. Tags: Research Source Type: research
Progerin sequestration of PCNA promotes replication fork collapse and mislocalization of XPA in laminopathy-related progeroid syndromes [Research]
In this study, the XPA mislocalization to DSBs occurred at stalled or collapsed replication forks, concurrent with a significant loss of PCNA at the forks, whereas PCNA efficiently bound to progerin. This PCNA sequestration likely exposed ds-ssDNA junctions at replication forks for XPA binding. Depletion of XPA or progerin each significantly restored PCNA at replication forks. Our results suggest that although PCNA is much more competitive than XPA in binding replication forks, PCNA sequestration by progerin may shift the equilibrium to favor XPA binding. Furthermore, we demonstrated that progerin-induced apoptosis could b...
Source: FASEB Journal - August 31, 2017 Category: Biology Authors: Hilton, B. A., Liu, J., Cartwright, B. M., Liu, Y., Breitman, M., Wang, Y., Jones, R., Tang, H., Rusinol, A., Musich, P. R., Zou, Y. Tags: Research Source Type: research
Human neutrophil elastase induces endothelial cell apoptosis by activating the PERK-CHOP branch of the unfolded protein response [Research]
Human neutrophil elastase impacts on atherosclerotic plaque stability by inducing apoptosis in endothelial cells. Our aim was to investigate the proapoptotic mechanism of elastase on endothelial cells and to evaluate the presence of elastase in human plaque material. Human endothelial cells were treated with purified human neutrophil elastase. Apoptosis was assayed by capsase-3/7 activation, TUNEL, and sub-G1 assay. Activation of unfolded protein response (UPR) effector molecules binding Ig protein, soluble X-binding protein-1, protein kinase RNA-like ER kinase (PERK), and C/EBP-homologous protein (CHOP) was analyzed by RT...
Source: FASEB Journal - August 31, 2017 Category: Biology Authors: Grechowa, I., Horke, S., Wallrath, A., Vahl, C.-F., Dorweiler, B. Tags: Research Source Type: research
Differential regulation of renal Klotho and FGFR1 in normal and uremic rats [Research]
In renal failure, hyperphosphatemia occurs despite a marked elevation in serum fibroblast growth factor (FGF)-23. Abnormal regulation of the FGFR1-Klotho receptor complex may cause a resistance to the phosphaturic action of FGF23. The purpose of the present study was to investigate the regulation of renal Klotho and FGF receptor (FEFR)-1 in healthy and uremic rats induced by 5/6 nephrectomy. In normal rats, the infusion of rat recombinant FGF23 enhanced phosphaturia and increased renal FGFR1 expression; however, Klotho expression was reduced. Uremic rats on a high-phosphate (HP) diet presented hyperphosphatemia with marked...
Source: FASEB Journal - August 31, 2017 Category: Biology Authors: Munoz-Castaneda, J. R., Herencia, C., Pendon-Ruiz de Mier, M. V., Rodriguez-Ortiz, M. E., Diaz-Tocados, J. M., Vergara, N., Martinez-Moreno, J. M., Salmeron, M. D., Richards, W. G., Felsenfeld, A., Kuro-O, M., Almaden, Y., Rodriguez, M. Tags: Research Source Type: research
Bile acids deoxycholic acid and ursodeoxycholic acid differentially regulate human {beta}-defensin-1 and -2 secretion by colonic epithelial cells [Research]
Bile acids and epithelial-derived human β-defensins (HβDs) are known to be important factors in the regulation of colonic mucosal barrier function and inflammation. We hypothesized that bile acids regulate colonic HβD expression and aimed to test this by investigating the effects of deoxycholic acid (DCA) and ursodeoxycholic acid on the expression and release of HβD1 and HβD2 from colonic epithelial cells and mucosal tissues. DCA (10–150 µM) stimulated the release of both HβD1 and HβD2 from epithelial cell monolayers and human colonic mucosal tissue in vitro. In contrast, urso...
Source: FASEB Journal - August 31, 2017 Category: Biology Authors: Lajczak, N. K., Saint-Criq, V., ODwyer, A. M., Perino, A., Adorini, L., Schoonjans, K., Keely, S. J. Tags: Research Source Type: research
PHD3 is a transcriptional coactivator of HIF-1{alpha} in nucleus pulposus cells independent of the PKM2-JMJD5 axis [Research]
The role of prolyl hydroxylase (PHD)-3 as a hypoxia inducible factor (HIF)-1α cofactor is controversial and remains unknown in skeletal tissues. We investigated whether PHD3 controls HIF-1 transcriptional activity in nucleus pulposus (NP) cells through the pyruvate kinase muscle (PKM)-2-Jumonji domain–containing protein (JMJD5) axis. PHD3–/– mice (12.5 mo old) showed increased incidence of intervertebral disc degeneration with a concomitant decrease in expression of the HIF-1α targets VEGF-A, glucose transporter-1, and lactate dehydrogenase A. PHD3 silencing decreased hypoxic activation o...
Source: FASEB Journal - August 31, 2017 Category: Biology Authors: Schoepflin, Z. R., Silagi, E. S., Shapiro, I. M., Risbud, M. V. Tags: Research Source Type: research
Sphingomyelin synthase 2 deficiency inhibits the induction of murine colitis-associated colon cancer [Research]
Sphingomyelin synthase 2 (SMS2) is the synthetic enzyme of sphingomyelin (SM), which regulates membrane fluidity and microdomain structure. SMS2 plays a role in LPS-induced lung injury and inflammation; however, its role in inflammation-mediated tumorigenesis is unclear. We investigated the effect of SMS2 deficiency on dextran sodium sulfate (DSS)–induced murine colitis and found inhibition of DSS-induced inflammation in SMS2-deficient (SMS2–/–) mice. DSS treatment induced a significant increase in ceramide levels, with a decrease of SM levels in SMS2–/– colon tissue, and demonstrated attenuat...
Source: FASEB Journal - August 31, 2017 Category: Biology Authors: Ohnishi, T., Hashizume, C., Taniguchi, M., Furumoto, H., Han, J., Gao, R., Kinami, S., Kosaka, T., Okazaki, T. Tags: Research Source Type: research
Cystic fibrosis transmembrane conductance regulator mediates tenogenic differentiation of tendon-derived stem cells and tendon repair: accelerating tendon injury healing by intervening in its downstream signaling [Research]
Tendons are a mechanosensitive tissue, which enables them to transmit to bone forces that are derived from muscle. Patients with tendon injuries, such as tendinopathy or tendon rupture, were often observed with matrix degeneration, and the healing of tendon injuries remains a challenge as a result of the limited understanding of tendon biology. Our study demonstrates that the stretch-mediated activation channel, cystic fibrosis transmembrane conductance regulator (CFTR), was up-regulated in tendon-derived stem cells (TDSCs) during tenogenic differentiation under mechanical stretching. Tendon tissues in CFTR-dysfunctional D...
Source: FASEB Journal - August 31, 2017 Category: Biology Authors: Liu, Y., Xu, J., Xu, L., Wu, T., Sun, Y., Lee, Y.-W., Wang, B., Chan, H.-C., Jiang, X., Zhang, J., Li, G. Tags: Research Source Type: research
Lysyl oxidase overexpression accelerates cardiac remodeling and aggravates angiotensin II-induced hypertrophy [Research]
Lysyl oxidase (LOX) controls matrix remodeling, a key process that underlies cardiovascular diseases and heart failure; however, a lack of suitable animal models has limited our knowledge with regard to the contribution of LOX to cardiac dysfunction. Here, we assessed the impact of LOX overexpression on ventricular function and cardiac hypertrophy in a transgenic LOX (TgLOX) mouse model with a strong cardiac expression of human LOX. TgLOX mice exhibited high expression of the transgene in cardiomyocytes and cardiofibroblasts, which are associated with enhanced LOX activity and H2O2 production and with cardiofibroblast repr...
Source: FASEB Journal - August 31, 2017 Category: Biology Authors: Galan, M., Varona, S., Guadall, A., Orriols, M., Navas, M., Aguilo, S., de Diego, A., Navarro, M. A., Garcia-Dorado, D., Rodriguez-Sinovas, A., Martinez-Gonzalez, J., Rodriguez, C. Tags: Research Source Type: research
MiR-2392 suppresses metastasis and epithelial-mesenchymal transition by targeting MAML3 and WHSC1 in gastric cancer [Research]
MicroRNAs have emerged as essential regulators of various cellular processes. We identified the role and underlying mechanisms of miR-2392 in gastric cancer (GC) metastasis. MiR-2392 was down-regulated in GC cell lines and tissues, and overexpression of miR-2392 significantly inhibited GC invasion and metastasis in vitro and in vivo. We identified MAML3 and WHSC1 as novel targets of miR-2392, and knockdown of MAML3 and WHSC1 had the same antimetastatic effect as that of miR-2392 in GC cells. These effects were clinically relevant, as low miR-2392 expression was correlated with high MAML3 and WHSC1 expression and poor survi...
Source: FASEB Journal - August 31, 2017 Category: Biology Authors: Li, J., Li, T., Lu, Y., Shen, G., Guo, H., Wu, J., Lei, C., Du, F., Zhou, F., Zhao, X., Nie, Y., Fan, D. Tags: Research Source Type: research
Small GTPase Rab1B is associated with ATG9A vesicles and regulates autophagosome formation [Research]
ATG9 is a membrane protein that is essential for autophagy and is considered to be directly involved in the early steps of autophagosome formation. Yeast Atg9 is mainly localized to small vesicles (Atg9 vesicles), whereas mammalian ATG9A is reportedly localized to the trans-Golgi network, the endosomal compartment, and other unidentified membrane structures. To dissect the ATG9A-containing membranes, we examined the subcellular localization of ATG9A and performed immunoisolation of those membranes. ATG9A-green fluorescent protein in human culture cells was observed as numerous puncta that move rapidly throughout the cytopl...
Source: FASEB Journal - August 31, 2017 Category: Biology Authors: Kakuta, S., Yamaguchi, J., Suzuki, C., Sasaki, M., Kazuno, S., Uchiyama, Y. Tags: Research Source Type: research
Astronaut ophthalmic syndrome [Hypothesis]
During and after missions on the International Space Station, some astronauts experience ophthalmic changes, including choroidal folds, optic disc edema, cotton-wool spots, globe flattening, and refraction changes. Astronauts with ophthalmic issues had significantly higher plasma concentrations of metabolites that are associated with the 1-carbon metabolic pathway than those without ophthalmic issues. We hypothesized that genetic differences might explain the metabolite differences. Indeed, genetics and B vitamin status were significant predictors of ophthalmic issues. We now have developed a hypothesis regarding the mecha...
Source: FASEB Journal - August 31, 2017 Category: Biology Authors: Zwart, S. R., Gibson, C. R., Gregory, J. F., Mader, T. H., Stover, P. J., Zeisel, S. H., Smith, S. M. Tags: Hypothesis Source Type: research
