Impaired integrin α5 /ß1 -mediated hepatocyte growth factor release by stellate cells of the aged liver.

Hepatic blood flow and sinusoidal endothelial fenestration decrease during aging. Consequently, fluid mechanical forces are reduced in the space of Disse where hepatic stellate cells (HSC) have their niche. We provide evidence that integrin α5 /ß1 is an important mechanosensor in HSC involved in shear stress-induced release of hepatocyte growth factor (HGF), an essential inductor of liver regeneration which is impaired during aging. The expression of the integrin subunits α5 and ß1 decreases in liver and HSC from aged rats. CRISPR/Cas9-mediated integrin α5 and ß1 knockouts in isolated HSC lead to lowered HGF release and impaired cellular adhesion. Fluid mechanical forces increase integrin α5 and laminin gene expression whereas integrin ß1 remains unaffected. In the aged liver, laminin ß2 and γ1 protein chains as components of laminin-521 are lowered. The integrin α5 knockout in HSC reduces laminin expression via mechanosensory mechanisms. Culture of HSC on nanostructured surfaces functionalized with laminin-521 enhances Hgf expression in HSC, demonstrating that these ECM proteins are critically involved in HSC function. During aging, HSC acquire a senescence-associated secretory phenotype and lower their growth factor expression essential for tissue repair. Our findings suggest that impaired mechanosensing via integrin α5 /ß1 in HSC contributes to age-related reduction of ECM and HGF release that could affect liver regeneration.

Laminin-521 promotes quiescence in isolated stellate cells from rat liver.

The laminin α5 protein chain is an element of basement membranes and important to maintain stem cells. Hepatic stellate cells (HSC) are liver-resident mesenchymal stem cells, which reside in a quiescent state on a basement membrane-like structure in the space of Dissé. In the present study, laminin α5 chain was detected in the space of Dissé of normal rat liver. Since HSC are critical for liver regeneration and can contribute to fibrosis in chronic liver diseases, the effect of laminins on HSC maintenance was investigated. Therefore, isolated rat HSC were seeded on uncoated polystyrene (PS) or PS coated with either laminin-521 (PS/LN-521) or laminin-211 (PS/LN-211). PS/LN-521 improved HSC adhesion and better preserved their retinoid stores as well as quiescence- and stem cell-associated phenotype, whereas HSC on PS/LN-211 or PS developed into myofibroblasts-like cells. To improve the homogeneity as well as the presentation of laminin molecules on the culture surface to HSC, laminin-functionalized, gold-nanostructured glass surfaces were generated. This approach further enhanced the expression of quiescence-associated genes in HSC. In conclusion, the results indicate that LN-521 supports the quiescent state of HSC and laminin α5 can be regarded as an important element of their niche in the space of Dissé.

Visual pop-out in barn owls: Human-like behavior in the avian brain.

Visual pop-out is a phenomenon by which the latency to detect a target in a scene is independent of the number of other elements, the distractors. Pop-out is an effective visual-search guidance that occurs typically when the target is distinct in one feature from the distractors, thus facilitating fast detection of predators or prey. However, apart from studies on primates, pop-out has been examined in few species and demonstrated thus far in rats, archer fish, and pigeons only. To fill this gap, here we study pop-out in barn owls. These birds are a unique model system for such exploration because their lack of eye movements dictates visual behavior dominated by head movements. Head saccades and interspersed fixation periods can therefore be tracked and analyzed with a head-mounted wireless microcamera--the OwlCam. Using this methodology we confronted two owls with scenes containing search arrays of one target among varying numbers (15-63) of similar looking distractors. We tested targets distinct either by orientation (Experiment 1) or luminance contrast (Experiment 2). Search time and the number of saccades until the target was fixated remained largely independent of the number of distractors in both experiments. This suggests that barn owls can exhibit pop-out during visual search, thus expanding the group of species and brain structures that can cope with this fundamental visual behavior. The utility of our automatic analysis method is further discussed for other species and scientific questions.