Proteoglycan and collagen expression during human air conducting system development

The thymus in vertebrates plays a critical role in producing functionally competent T-lymphocytes. Phylogenetically, the thymus emerges early during evolution in jawed cartilaginous fish, and it is usually a bilateral organ placed subcutaneously at the dorsal commissure of the operculum. In this review, we summarize the current understanding of the thymus localization, histology studies, cell composition, and function in teleost fishes. Furthermore, we consider environmental factors that affect thymus development, such as seasonal changes, photoperiod, water temperature fluctuations and hormones. Further analysis of the thymus cell distribution and function will help us understand how key stages for developing functional T cells occur in fish, and how thymus dynamics can be modulated by external factors like photoperiod. Overall, the information presented here helps identify the knowledge gaps and future steps needed for a better understanding of the immunobiology of fish thymus.

Vascularization and blood cell circulation are crucial steps during lung development. However, how blood vessels are generated and when lung circulation is initiated is still a matter of debate. A morpho‐functional analysis of pulmonary vasculature was done using human lung samples between 31 and 56 days post‐fertilization (pf). The immunolocalization and expression of CD31, CD34, FLT‐1, KDR and the vascular growth factor (VEGF) were investigated. The results showed that at day 31 pf, a capillary plexus is already installed, and a few primitive erythroblasts were seen for the first time within the lumen of some blood vessels. Around day 45 pf, an increase in the amount of primitive erythroblasts was detected in the parenchyma surrounding the distal segment of the bronchial tree. The expression of FLT‐1, KDR, CD31 and CD34 was observed in endothelial cells of the capillary plexus and the VEGF was detected in the endodermal epithelium. Our results support the hypothesis that the initial formation of the capillary plexus around the tip of the growing airway bud occurs by vasculogenesis, probably regulated by VEGF and KDR. We also showed a very early onset of blood circulation, starting from day 34 pf, concomitant with the generation of new lung buds. In addition, the increasing number of primitive erythroblasts from week 6 onward, associated with a change in the shape of the blood vessels, suggests a remodeling process and that the generation of new distal vessels at the tip of the lung bud occurs mainly by a process of angiogenesis.

The metabolite 2-methoxyestradiol (2ME) is an endogenous estrogen metabolite with potential therapeutic properties in reproductive cancers. However, the molecular mechanisms by which 2ME exerts its anticancer activity are not well elucidated. The purpose of this study was to determine the molecular signals associated with the apoptotic effects of 2ME in a human endometrial cancer cell line. Ishikawa cells were treated with non-apoptotic (0.1 µM) or apoptotic concentrations (5 µM) of 2ME, and 12 hours later mRNA levels for Scd2, Snx6, and Spon1 were determined by real-time PCR. We then investigated by immunofluorescence and Western blot the expression and distribution of F-spondin, encoded by Spon1, in Ishikawa cells treated with 2ME 5 µM at 6, 12, or 24 h after treatment. The role of estrogen receptors (ER) in the effect of 2ME on the Spon1 level was also investigated. Finally, we examined whether 2ME 5 µM induces cell death in Ishikawa cells pre-incubated with a neutralizing F-spondin antibody. Non-apoptotic or apoptotic concentrations of 2ME decreased Scd2 and increased Snx6. However, Spon1 was only increased with the 2ME apoptotic concentration. F-spondin protein was also increased at 12 and 24 h after 2ME treatment, while 2ME-induced Spon1 increase was independent of ER. Neutralization of F-spondin blocked the effect of 2ME on the cell viability. These results show that F-spondin signaling is one of the components in the apoptotic effects of 2ME on Ishikawa cells and provide experimental evidence underlying the mechanism of action of this estrogen metabolite on cancer cells.