Receptor for advanced glycation end‐products is a marker of type I lung alveolar cells

Shirasawa, Madoka; Fujiwara, Naoyuki; Hirabayashi, Susumu; Ohno, Hideki; Iida, Junko; Makita, Koshi; Hata, Yoshinobu

doi:10.1111/j.1356-9597.2004.00712.x

Cited by 174 publications

(170 citation statements)

References 20 publications

(30 reference statements)

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“…RAGE expression has been shown to correlate with this differentiation. 13 Thus, loss of RAGE expression may result in decreased binding of the basement membrane and increased susceptibility to alveolar injury and/or prevent the proper re-epithelialization of alveoli during IPF pathogenesis.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, RAGE expression is essential for type I alveolar epithelial cell morphology and transdifferentiation of type II cells, both of which are believed to play a role in the maintenance of normal lung physiology and repair. 13,14,19,20 Therefore, we investigated the hypothesis that RAGE plays a central role in IPF pathogenesis by using animal models of pulmonary fibrosis, human IPF tissues, and RAGE-null mice.…”

mentioning

confidence: 99%

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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

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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.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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

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“…After 2 days in culture, these cells lose the expression of AT2 markers and up-regulate markers of type 1 cell differentiation, such as T1␣ and receptor for advanced glycation end products (RAGE) (37,38) (Fig. 1A).…”

Section: Endogenous Activation Of ␤-Catenin/tcf Signaling Activity Inmentioning

confidence: 99%

β-Catenin/T-cell Factor Signaling Is Activated during Lung Injury and Promotes the Survival and Migration of Alveolar Epithelial Cells

Flozak

Lam

Russell

et al. 2010

Journal of Biological Chemistry

112

117

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The Wnt/␤-catenin signaling cascade activates genes that allow cells to adopt particular identities throughout development. In adult self-renewing tissues like intestine and blood, activation of the Wnt pathway maintains a progenitor phenotype, whereas forced inhibition of this pathway promotes differentiation. In the lung alveolus, type 2 epithelial cells (AT2) have been described as progenitors for the type 1 cell (AT1), but whether AT2 progenitors use the same signaling mechanisms to control differentiation as rapidly renewing tissues is not known. We show that adult AT2 cells do not exhibit constitutive ␤-catenin signaling in vivo, using the AXIN2

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“…3,4,6 In healthy animals and humans, RAGE expression is most prominent in the lung, including alveolar type I and type II epithelial cells, alveolar macrophage, endothelia and some bronchiolar epithelia. [7][8][9][10] The activation of RAGE by its ligands triggers several signal transduction pathways involved in acute and chronic inflammation, including the NFκB and MAP kinase pathway. 1,11,12 In turn, NFκB upregulates RAGE expression, leading to the amplification of the pro-inflammatory cascade.…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics and lung distribution of a humanized anti-RAGE antibody in wild-type and RAGE^-/-mice

Vugmeyster

DeFranco

Pittman

et al. 2010

mAbs

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Receptor for advanced glycation end‐products is a marker of type I lung alveolar cells

Cited by 174 publications

References 20 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

β-Catenin/T-cell Factor Signaling Is Activated during Lung Injury and Promotes the Survival and Migration of Alveolar Epithelial Cells

Pharmacokinetics and lung distribution of a humanized anti-RAGE antibody in wild-type and RAGE^-/-mice

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Receptor for advanced glycation end‐products is a marker of type I lung alveolar cells

Cited by 174 publications

References 20 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

β-Catenin/T-cell Factor Signaling Is Activated during Lung Injury and Promotes the Survival and Migration of Alveolar Epithelial Cells

Pharmacokinetics and lung distribution of a humanized anti-RAGE antibody in wild-type and RAGE-/-mice

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Pharmacokinetics and lung distribution of a humanized anti-RAGE antibody in wild-type and RAGE^-/-mice