Functional Wnt Signaling Is Increased in Idiopathic Pulmonary Fibrosis

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease, characterized by distorted lung architecture and loss of respiratory function. Alveolar epithelial cell injury and hyperplasia, enhanced extracellular matrix deposition, and (myo)fibroblast activation are features of IPF. Wnt/beta-catenin signaling has been shown to determine epithelial cell fate during development. As aberrant reactivation of developmental signaling pathways has been suggested to contribute to IPF pathogenesis, we hypothesized that Wnt/beta-catenin signaling is activated in epithelial cells in IPF. Thus, we quantified and localized the expression and activity of the Wnt/beta-catenin pathway in IPF. METHODOLOGY/PRINCIPAL FINDINGS: The expression of Wnt1, 3a, 7b, and 10b, the Wnt receptors Fzd1-4, Lrp5-6, as well as the intracellular signal transducers Gsk-3beta, beta-catenin, Tcf1, 3, 4, and Lef1 was analyzed in IPF and transplant donor lungs by quantitative real-time (q)RT-PCR. Wnt1, 7b and 10b, Fzd2 and 3, beta-catenin, and Lef1 expression was significantly increased in IPF. Immunohistochemical analysis localized Wnt1, Wnt3a, beta-catenin, and Gsk-3beta expression largely to alveolar and bronchial epithelium. This was confirmed by qRT-PCR of primary alveolar epithelial type II (ATII) cells, demonstrating a significant increase of Wnt signaling in ATII cells derived from IPF patients. In addition, Western blot analysis of phospho-Gsk-3beta, phospho-Lrp6, and beta-catenin, and qRT-PCR of the Wnt target genes cyclin D1, Mmp 7, or Fibronectin 1 demonstrated increased functional Wnt/beta-catenin signaling in IPF compared with controls. Functional in vitro studies further revealed that Wnt ligands induced lung epithelial cell proliferation and (myo)fibroblast activation and collagen synthesis. CONCLUSIONS/SIGNIFICANCE: Our study demonstrates that the Wnt/beta-catenin pathway is expressed and operative in adult lung epithelium. Increased Wnt/beta-catenin signaling may be involved in epithelial cell injury and hyperplasia, as well as impaired epithelial-mesenchymal cross-talk in IPF. Thus, modification of Wnt signaling may represent a therapeutic option in IPF

The dynamics of expanding mangroves in New Zealand

In contrast to the global trend of mangrove decline, New Zealand mangroves are rapidly expanding, facilitated by elevated sediment inputs in coastal waters as a consequence of large-scale land use changes following European settlement. New Zealand mangroves are at the southern limit of the global mangrove extent, which limits the tree height of Avicennia marina var. australasica, the only mangrove species present. Mangroves in New Zealand thrive in the sheltered environments of infilling drowned river valleys with abundant supply of fine terrigenous sediments, showing various stages of mangrove succession and expansion dynamics. Bio-physical interactions and carbon dynamics in these expanding temperate mangrove systems show similarities to, but also differ from those in tropical mangrove forests, for instance due to the limited height and complexity of the mangrove communities. Likewise, ecosystem services provided by New Zealand mangroves deviate from those offered by tropical mangroves. In particular, the association of mangrove expansion with the accumulation of (the increased supply of) fine sediments and the consequent change of estuarine ecosystems, has provoked a negative perception of mangrove expansion and subsequently led to mangrove clearance. Over recent decades, a body of knowledge has been developed regarding the planning and decision making relating to mangrove removal, yet there are still effects that are unknown, for example with respect to the post-clearance recovery of the original sandflat ecosystems. In this chapter we discuss the dynamics of New Zealand’s expanding mangroves from a range of viewpoints, with the aim of elucidating the possible contributions of expanding mangroves to coastal ecosystem services, now and in the future. This chapter also reviews current policies and practice regarding mangrove removal in New Zealand and addresses the (un)known effects of mangrove clearance. These combined insights may contribute to the development of integrated coastal management strategies that recognise the full potential of expanding mangrove ecosystems

Effect of sewage discharge in Spisula subtruncata (da Costa 1778) populations

Sewage discharge is a common source of pollution in coastal marine. Spisula subtruncata (da Costa, 1778) is a common filter feeding bivalve in the Castellon coast (north-western Mediterranean Sea). In the Spisula community of this area several municipal treatment plants dump treated water. We sampled in five locations affected by sewage dicharge. Van Veen grab samples were obtained for the study of the bivalve population and to characterize the sediment. The sewage dicharges studied affect Spisula populations. In the stations near the outfalls the abundance and the average size of S. subtruncata decreases. However this effects do not show correlation with characteristics of sediment, such us granulometry or pH.CONSOMAR S.A. and Entitat de Sanejament d'Aigües