Type II Alveolar Epithelial Cells in Lung Express Receptor for Advanced Glycation End Products (RAGE) Gene

Katsuoka, Fumiki; Kawakami, Yasushi; Arai, Takashi; Imuta, Hiroyuki; Fujiwara, Masachika; Kanma, Hiroshi; Yamashita, Kamejiro

doi:10.1006/bbrc.1997.7263

Cited by 94 publications

(77 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Similar to RAGE mRNA and sRAGE protein, mRAGE protein is found at the highest levels in the lung. The relatively abundant expression of pulmonary mRAGE and sRAGE in the normal lung observed by us as well as others 6,7,33 suggests that it plays a homeostatic role unique to the lung. Thus, alterations in mRAGE and sRAGE expression may be a factor in pulmonary diseases such as pulmonary fibrosis.…”

Section: Membrane Rage Is Highly Expressed In Adult Mouse Lungssupporting

confidence: 60%

A Role for the Receptor for Advanced Glycation End Products in Idiopathic Pulmonary Fibrosis

Englert

Hanford

Kaminski

et al. 2008

The American Journal of Pathology

206

220

View full text Add to dashboard Cite

Idiopathic pulmonary fibrosis (IPF) is a severely debilitating disease associated with a dismal prognosis. There are currently no effective therapies for IPF, thus the identification of novel therapeutic targets is greatly needed. The receptor for advanced glycation end products (RAGE) is a member of the immunoglobulin superfamily of cell surface receptors whose activation has been linked to various pathologies. In healthy adult animals, RAGE is expressed at the highest levels in the lung compared to other tissues. To investigate the hypothesis that RAGE is involved in IPF pathogenesis, we have examined its expression in two mouse models of pulmonary fibrosis and in human tissue from IPF patients. In each instance we observed a depletion of membrane RAGE and its soluble (decoy) isoform, sRAGE, in fibrotic lungs. In contrast to other diseases in which RAGE signaling promotes pathology, immunohistochemical and hydroxyproline quantification studies on aged RAGEnull mice indicate that these mice spontaneously develop pulmonary fibrosis-like alterations. Furthermore, when subjected to a model of pulmonary fibrosis, RAGE-null mice developed more severe fibrosis, as measured by hydroxyproline assay and histological scoring, than wild-type controls. Combined with data from other studies on mouse models of pulmonary fibrosis and human IPF tissues indicate that loss of RAGE contributes to IPF pathogenesis. Idiopathic pulmonary fibrosis (IPF) is a debilitating disease with a dismal prognosis. Mean survival time after biopsy-confirmed diagnosis is 3 to 5 years.1,2 Traditional therapy involves the use of corticosteroids as nonspecific anti-inflammatory agents. This treatment produces an objective response in only 10 to 20% of patients and has a minimal effect on the fatal course of IPF.2-4 Thus, the need for new therapeutic modalities is evident.The receptor for advanced glycation end products (RAGE) is a member of the immunoglobulin super family of cell surface receptors. 5 In most healthy adult animal tissues, RAGE is expressed at low to undetectable levels.6,7 Activation of membrane-bound RAGE (mRAGE) by its ligands (including advanced glycation end products, HMGB1/amphoterin, S100/calgranulins, and amyloid-␤ peptide) often leads to proinflammatory signaling as well as up-regulation of RAGE itself.8 This signaling by mRAGE is believed to play an important role in disease progression for several nonpulmonary diseases, including various diabetic complications, chronic inflammation, and Alzheimer's disease, among others. 9,10 In contrast to other healthy adult tissues, RAGE mRNA and sRAGE protein are highly expressed in normal adult lungs. 6,7,11 Most recently it has been suggested that RAGE is a marker of type I alveolar epithelial cells 12 and type II alveolar epithelial cell transdifferentiation, a component of pulmonary re-epithelialization and repair.

show abstract

Section: Membrane Rage Is Highly Expressed In Adult Mouse Lungssupporting

confidence: 60%

A Role for the Receptor for Advanced Glycation End Products in Idiopathic Pulmonary Fibrosis

Englert

Hanford

Kaminski

et al. 2008

The American Journal of Pathology

206

220

View full text Add to dashboard Cite

show abstract

“…Expression is localized to alveolar type II cells (112) and on the basolateral membranes of the alveolar type I epithelial cells (113). The physiological relevance of the high expression in these cells is unknown.…”

Section: The Receptor For Advanced Glycation End Products (Rage)mentioning

confidence: 99%

HMGB1 and RAGE in Inflammation and Cancer

Sims¹,

Rowe²,

Rietdijk

et al. 2010

Annu. Rev. Immunol.

1,226

1,096

View full text Add to dashboard Cite

The immune system has evolved to respond not only to pathogens, but also to signals released from dying cells. Cell death through necrosis induces inflammation, whereas apoptotic cell death provides an important signal for tolerance induction. High mobility group box 1 (HMGB1) is a DNA-binding nuclear protein, released actively following cytokine stimulation as well as passively during cell death; it is the prototypic damage-associated molecular pattern (DAMP) molecule and has been implicated in several inflammatory disorders. HMGB1 can associate with other molecules, including TLR ligands and cytokines, and activates cells through the differential engagement of multiple surface receptors including TLR2, TLR4, and RAGE. RAGE is a multiligand receptor that binds structurally diverse molecules, including not only HMGB1, but also S100 family members and amyloid-β. RAGE activation has been implicated in sterile inflammation as well as in cancer, diabetes, and Alzheimer's disease. While HMGB1 through interactions with TLRs may also be important, this review focuses on the role of the HMGB1-RAGE axis in inflammation and cancer.

show abstract

“…Immmunoelectron microscopic studies demonstrate that RAGE is expressed on the basal surface of ATI cells in the lung [41,42]. However, mRNA transcripts for RAGE have also been detected in ATII cells in the lung [43]. The role of RAGE in ATI cells is unknown.…”

Section: Group II Alveolar Epithelial Type I Cell-selective Proteinsmentioning

confidence: 99%

The use of alveolar epithelial type I cell-selective markers to investigate lung injury and repair

McElroy

Kasper²

2004

European Respiratory Journal

115

View full text Add to dashboard Cite

Ultrastructural studies demonstrate that alveolar epithelial type I cell damage is frequently observed in acute and chronic lung diseases.This article discusses the use of cell-selective proteins as markers for the investigation of injury and repair of the alveolar epithelium. The utility of proteins specific to alveolar epithelial type I cells as diagnostic markers of alveolar epithelial injury in acute lung injury is considered, and expression of proteins selective for alveolar epithelial type I cells in lungs following injury and in fibrosis are discussed. Eur Respir J 2004; 24: 664-673.

show abstract

Type II Alveolar Epithelial Cells in Lung Express Receptor for Advanced Glycation End Products (RAGE) Gene

Cited by 94 publications

References 5 publications

A Role for the Receptor for Advanced Glycation End Products in Idiopathic Pulmonary Fibrosis

A Role for the Receptor for Advanced Glycation End Products in Idiopathic Pulmonary Fibrosis

HMGB1 and RAGE in Inflammation and Cancer

The use of alveolar epithelial type I cell-selective markers to investigate lung injury and repair

Contact Info

Product

Resources

About