Distribution of Hepatocyte Growth Factor Activator Inhibitor Type 1 (HAI-1) in Human Tissues: Cellular Surface Localization of HAI-1 in Simple Columnar Epithelium and Its Modulated Expression in Injured and Regenerative Tissues

Abstract

SUMMARYWe used a specific monoclonal antibody to human hepatocyte growth factor activator inhibitor type 1 (HAI-1) in immunohistochemical procedures to determine the distribution and localization of HAI-1 in human tissues. In normal adult tissues, HAI-1 was predominantly expressed in the simple columnar epithelium of the ducts, tubules, and mucosal surface of various organs. In all cases, HAI-1 was localized predominantly on the cellular lateral (or basolateral) surface. By contrast, hepatocytes, acinar cells, endocrine cells, stromal mesenchymal cells, and inflammatory cells were hardly stainable with the antibody, and stratified squamous epithelium showed only faint immunoreactivity on the surface of cells of the basal layer. In the gastrointestinal tract, the surface epithelium was strongly stained. RNA blot analysis confirmed the presence of specific mRNA transcript in the gastrointestinal mucosa, and in situ hybridization revealed that HAI-1 mRNA showed a similar cellular distribution pattern. Although HAI-1 was not expressed in normal hepatocytes, strong immunoreactivity was observed on the epithelium of pseudo-bile ducts and on the surface of scattered hepatocytes in fulminant hepatitis. The enhanced expression was also noted in regenerating tubule epithelial cells of the kidney after infarction. We conclude that HAI-1 is preferentially expressed in the simple columnar epithelium of the mucosal surface and duct, that the predominant localization of HAI-1 is the cell surface, and that the expression of HAI-1 can be modulated by tissue injury and regeneration.

Membrane-Bound Serine Protease Inhibitor HAI-1 Is Required for Maintenance of Intestinal Epithelial Integrity

“…In humans, HAI-1/SPINT1 is expressed in most epithelial tissues, with the most abundant expression in the gastrointestinal tract and placental cytotrophoblasts, and its subcellular localization is predominantly basolateral in polarized epithelial cells. 4,5 The mouse HAI-1/ SPINT1 also shows expression patterns that are similar to those in humans. 6 Because of this similarity, the biological functions of HAI-1/SPINT1 in vivo have been studied in mice using Spint1 mutant mice.…”

Involvement of the cytoplasmic juxtamembrane region of matriptase in its exclusive localization to the basolateral membrane domain of Madin–Darby canine kidney epithelial cells

“…Indeed, when expressed alone in this cell line, matriptase was retained in the endoplasmic reticulum and Golgi apparatus. In addition, HAI-1 is known to be present on the basolateral membrane domain of simple epithelia in intact tissues (Kataoka et al 1999;Godiksen et al 2008). These observations raise the possibility that the localization of matriptase in simple epithelia depends on HAI-1.…”

Requirement of the activity of hepatocyte growth factor activator inhibitor type 1 for the extracellular appearance of a transmembrane serine protease matriptase in monkey kidney COS-1 cells

“…Hepatocyte growth factor (HGF) activator inhibitor type 1 (HAI-1) is a Kunitz-type serine protease inhibitor, which is strongly expressed in epithelial elements of organs (Shimomura et al 1997;Kataoka et al 1999). HAI-1 is expressed first as a membraneanchored form with a molecular mass of 66 kDa (refer to Fig.…”