Distribution and mRNA Expression of Tenascin-C in Developing Human Lung

Abstract

Tenascin-C is an extracellular matrix glycoprotein that is spatially expressed during organogenesis, in inflammatory and fibrotic disorders, and in neoplasms. The aim of this study was to analyze its expression in developing human lung tissues during pseudoglandular, canalicular, saccular, and alveolar periods corresponding to Weeks 12 to 40. Lung tissues were obtained at autopsy from 34 nonmalformed cases. An immunohistochemical analysis and a messenger RNA (mRNA) in situ hybridization method combined with light microscopy were used. The extent of tenascin-C immunoreactivity was scored as absent, low, moderate, or strong in and around different types of pulmonary cells. The immunohistochemical expression for tenascin-C was strong beneath the airway epithelium, especially at the sites of airway subdivision during Weeks 12 to 23, whereas its expression was moderate or weak underneath alveolar and bronchiolar epithelia between Weeks 24 and 40. The expression for tenascin-C was strong in the intima of veins, especially in the canalicular period, i.e., Weeks 17 to 28. A moderate or strong immunoreactivity for tenascin-C was also observed around chondrocytes in every case studied during all periods. The increased expression of tenascin-C mRNA was most often seen in the cells below the airway epithelium. Taken together, tenascin-C is expressed in human lung during all developmental periods, and its expression is especially strong below the airway epithelium at the sites of airway subdivision.

EngineeringDe NovoAssembly of Fetal Pulmonary Organoids

“…The critical role of TN-C in lung development in vivo has largely been deduced from histological studies 37,38,43 and embryonic lung explant cultures in the context of hypoxia 28 and TN-C gene deletion, 39 all of which demonstrated a positive regulatory role of TN-C in lung epithelial branching morphogenesis. Jones and colleagues demonstrated an indirect functional connection between TN-C and distal lung vascular development through the homeodomain transcription factor Prx-1, which is expressed in the mesenchyme and is required for pulmonary vascular development and TN-C gene expression.…”

“…Focal deposition patterns of TN-C indicate a role in FGF10/7/2-driven morphogenesis Given the known and implicated roles of TN-C in lung development, [37][38][39][40][41][42][43][44] we hypothesized that focal deposition of TN-C could provide pivotal cues for the spatial patterning of histiotypic endothelial and epithelial morphogenesis. Since the starting ECM is a simple, homogeneous type I collagen gel, the presence of TN-C and other ECM constituents, such as laminin (LN), is reflective of endogenous production by fetal pulmonary cells.…”

Reparative Capacity of Airway Epithelium Impacts Deposition and Remodeling of Extracellular Matrix

“…ECM deposition is controlled by the combined regulation of protein synthesis and degradation. Studies in human lung indicate that Tnc is expressed in cells of the subepithelial mesenchyme during development and in disease (35,36). In vitro studies also indicate that fibroblasts are a source of Tnc expression (37).…”

c-Kit immunoexpression delineates a putative endothelial progenitor cell population in developing human lungs

“…To distinguish mast cells from c-Kit ϩ fetal lung cells, we used double staining for c-Kit and mast cell tryptase, which is specifically expressed by human mast cells (39). In addition, we used anti-CD34 antibody to identify the endothelial cells (42); and anti-␣-smooth muscle actin (SMA) antibody to identify smooth muscle cells, myofibroblasts (16,25), and the vascular bed of the pulmonary artery and pulmonary vein (12,25).…”