Implications of hypoxia on mucosal barrier function.

J Karhausen; J C Ibla; S P Colgan

Home/Archive/PubMed

PubMed · 12839339

Implications of hypoxia on mucosal barrier function.

J Karhausen·J C Ibla·S P Colgan

View original source ↗Export metadata ↓

Abstract

Epithelial cells which line mucosal surfaces (e.g. lung, intestine) critically function as a semi-permeable barrier to the outside world. Mucosal organs are highly vascular with extensive metabolic demands, and for this reason, are particularly susceptible to diminished blood flow and resultant tissue hypoxia. Recent work from a number of groups have defined the critical molecular and cellular determinants of barrier function in hypoxic/ischemic tissues. Here, we will briefly highlight some of these studies from both a basic and clinical viewpoint and provide a perspective on future work related to tigh tjunction function in mucosal hypoxia.

Explore related subjects

Adherens Junctions Animals Cyclic AMP Response Element-Binding Protein DNA-Binding Proteins Gene Expression Regulation Humans Hypoxia Hypoxia-Inducible Factor 1 Hypoxia-Inducible Factor 1, alpha Subunit Intestinal Mucosa Kidney Lung Mucous Membrane Nuclear Proteins Transcription Factors Journal Article Review

Keep this discovery

Explore connections, maps & timelines

BibTeX RIS

J Karhausen, J C Ibla, S P Colgan. 2003. Implications of hypoxia on mucosal barrier function.. https://pubmed.ncbi.nlm.nih.gov/12839339/

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2007

Beyond the epithelium: cadherin function in fibrous connective tissues.

In fibrous connective tissues, fibroblasts are organized into syncytia, cellular networks that enable matrix remodeling and that are interconnected by intercellular adherens junctions (AJs). The AJs of fibroblasts are mediated by N-cadherin, a broadly expressed classical cadherin that is critically involved in developmental processes, wound healing and several diseases of mesenchymal tissues. In contrast to E-cadherin-dependent junctions of epithelia, the formation of AJs in fibrous connective tissues is relatively uncharacterized. Work over the last several years has documented an expanding list of molecules which function to regulate N-cadherin mediated junctions such as: Fer, PTP1B, cortactin, calcium, gelsolin, PIP5KIgamma, PIP2, and the Rho family of GTPases. We present an overview on the regulation of N-cadherin-mediated junction formation that highlights recent molecular advances in the field and rationalizes the roles of N-cadherin in connective tissue function.

Adherens Junctions↗

PubMed2007

Rap1: a key regulator in cell-cell junction formation.

Rap1 is a Ras-like small GTPase that is activated by many extracellular stimuli and strongly implicated in the control of integrin-mediated cell adhesion. Recent evidence indicates that Rap1 also plays a key role in formation of cadherin-based cell-cell junctions. Indeed, inhibition of Rap1 generates immature adherens junctions, whereas activation of Rap1 tightens cell-cell junctions. Interestingly, Rap1 guanine nucleotide exchange factors, such as C3G and PDZ-GEF, are directly linked to E-cadherin or to other junction proteins. Furthermore, several junction proteins, such as afadin/AF6 and proteins controlling the actin cytoskeleton, function as effectors of Rap1. These findings point to a role of Rap1 in spatial and temporal control of cell-cell junction formation.

Adherens Junctions↗

PubMed2007

Junction interaction in the seminiferous epithelium: regulatory roles of connexin-based gap junction.

Anchoring junction, tight junction (TJ), and gap junction (GJ) constitute three major junction types in mammalian testes. Connexin is the well-studied GJ protein. It forms the building block of connexon, which is composed of six connexin units. Connexon forms the functional GJ when pairing with counter-connexon from neighboring cells. In the testis, at least eleven connexins are associated with the Sertoli and germ cells of the seminiferous epithelium and the Leydig cells of the interstitium, modulating spermatogenesis and steroidogenesis, respectively. Significantly, connexins are recently speculated to act as regulators of other junctions in the testes using pan-connexin peptide model. This demonstrates that the loss of connexin function leads to a preferential degradation of occludin-based TJ, but not N-cadherin-based adherens junction (AJ), in the testis, despite the intermingled relationship of these three junctions at the site of blood-testis barrier. In the clinical aspects, connexins are shown to relate to male infertility and testicular dysfunctions. A panel of molecules and proteins and their associated protein kinases are actively participating in the regulation of connexin-mediated GJ and fine-tuning connexin-associated functions in the testis. Herein, we summarize the latest findings of connexins in the testis in the aspects of fertility, and testicular diseases, with emphasis on the unexplored roles of connexins in regulating other junction types. This can shed light on future studies in implicating the putative roles of connexins in the physiological functions of reproduction and the clinical aspects of male infertility. In addition, understanding the roles of connexins can advance the diagnosis and treatment of testicular dysfunction and infertility.

Adherens Junctions↗