Antifibrotic properties of receptor for advanced glycation end products in idiopathic pulmonary fibrosis

Ding, Hui; Ji, XiuHai; Chen, Ruhua; Ma, Tieliang; Tang, Zhengyang; Fu, Yan; Cai, Hourong

doi:10.1016/j.pupt.2015.10.010

Cited by 19 publications

(15 citation statements)

References 30 publications

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“…AGEs also have been shown to promote the endothelial to mesenchymal transition [59]. However, despite these studies showing a pro-fibrotic role for RAGE, there are studies that show the anti-fibrotic properties of RAGE or that a lack of RAGE is protective against bleomycin-induced lung fibrosis [60,61]. Therefore, the role of RAGE in fibrosis could be tissue-specific and/or dependent on the fibrosis causative factor(s).…”

Section: Discussionmentioning

confidence: 99%

AGE-RAGE interaction in the TGFβ2-mediated epithelial to mesenchymal transition of human lens epithelial cells

Raghavan

Nagaraj

2016

Glycoconj J

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Basement membrane (BM) proteins accumulate chemical modifications with age. One such modification is glycation, which results in the formation of advanced glycation endproducts (AGEs). In a previous study, we reported that AGEs in the human lens capsule (BM) promote the TGFβ2-mediated epithelial-to-mesenchymal transition (EMT) of lens epithelial cells, which we proposed as a mechanism for posterior capsule opacification (PCO) or secondary cataract formation. In this study, we investigated the role of a receptor for AGEs (RAGE) in the TGFβ2-mediated EMT in a human lens epithelial cell line (FHL124). RAGE was present in FHL124 cells, and its levels were unaltered in cells cultured on either native or AGE-modified BM or upon treatment with TGFβ2. RAGE overexpression significantly enhanced the TGFβ2-mediated EMT responses in cells cultured on AGE-modified BM compared with the unmodified matrix. In contrast, treatment of cells with a RAGE antibody or EN-RAGE (an endogenous ligand for RAGE) resulted in a significant reduction in the TGFβ2-mediated EMT response. This was accompanied by a reduction in TGFβ2-mediated Smad signaling and ROS generation. These results imply that the interaction of matrix AGEs with RAGE plays a role in the TGFβ2-mediated EMT of lens epithelial cells and suggest that the blockade of RAGE could be a strategy to prevent PCO and other age-associated fibrosis.

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Section: Discussionmentioning

confidence: 99%

AGE-RAGE interaction in the TGFβ2-mediated epithelial to mesenchymal transition of human lens epithelial cells

Raghavan

Nagaraj

2016

Glycoconj J

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“…JNK drives transcription of numerous key EMT genes (20). It has been reported that TGF-β1 induced JNK activation during EMT in idiopathic pulmonary fibrosis (21). In the present study, it was examined whether JNK signaling pathway has a critical role in the regulation of miR-145-5p-mediated EMT in NSCLC cells.…”

Section: Involvement Of Jnk Signaling In Mir-145-5p-induced Emt Supprmentioning

confidence: 90%

miR‑145‑5p inhibits epithelial‑mesenchymal transition via the JNK signaling pathway by targeting MAP3K1 in non‑small cell lung cancer cells

et al. 2017

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Abstract. Lung cancer is one of the most common types of tumors and the leading cause of cancer-associated mortality in the world. Additionally, non-small cell lung cancer (NSCLC) accounts for ~80% of all lung cancer cases. Epithelialmesenchymal transition (EMT) is an important cell biological process, which is associated with cancer migration, metastasis, asthma and fibrosis in the lung. In the present study, it was revealed that miR-145-5p was able to suppress EMT by inactivating the c-Jun N-terminal kinase (JNK) signaling pathway in NSCLC cells. Mitogen-activated protein kinase kinase kinase 1 (MAP3K1) was predicted and confirmed to be a novel target of miR-145-5p. Overexpression of MAP3K1 was able to reverse the inhibition of EMT induced by miR-145-5p via the JNK signaling pathway. Overall, the results revealed that miR-145-5p inhibits EMT via the JNK signaling pathway by targeting MAP3K1 in NSCLC cells.

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“…RAGE KO mice are protected from bleomycin-induced injury, and AT2 cells from RAGE KO mice do not undergo HMGB1-induced EMT as wild-type cells do [114]. On the other hand, stimulation of AT2-like cells (A549) with TGF- β and proinflammatory cytokines, induced cytoskeletal rearrangements characteristic of EMT, and decreases RAGE expression [110,117]. The role of RAGE in EMT remains a question, as it is unclear if it is required for EMT or if its deficiency promotes EMT.…”

Section: Rage In Pulmonary Diseasesmentioning

confidence: 99%

All the “RAGE” in lung disease: The receptor for advanced glycation endproducts (RAGE) is a major mediator of pulmonary inflammatory responses

Oczypok

Perkins

Oury

2017

Paediatric Respiratory Reviews

159

185

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SUMMARY The receptor for advanced glycation endproducts (RAGE) is a pro-inflammatory pattern recognition receptor (PRR) that has been implicated in the pathogenesis of numerous inflammatory diseases. It was discovered in 1992 on endothelial cells and was named for its ability to bind advanced glycation endproducts and promote vascular inflammation in the vessels of patients with diabetes. Further studies revealed that RAGE is most highly expressed in lung tissue and spurred numerous explorations into RAGE’s role in the lung. These studies have found that RAGE is an important mediator in allergic airway inflammation (AAI) and asthma, pulmonary fibrosis, lung cancer, chronic obstructive pulmonary disease (COPD), acute lung injury, pneumonia, cystic fibrosis, and bronchopulmonary dysplasia. RAGE has not yet been targeted in the lungs of paediatric or adult clinical populations, but the development of new ways to inhibit RAGE is setting the stage for the emergence of novel therapeutic agents for patients suffering from these pulmonary conditions.

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Antifibrotic properties of receptor for advanced glycation end products in idiopathic pulmonary fibrosis

Cited by 19 publications

References 30 publications

AGE-RAGE interaction in the TGFβ2-mediated epithelial to mesenchymal transition of human lens epithelial cells

AGE-RAGE interaction in the TGFβ2-mediated epithelial to mesenchymal transition of human lens epithelial cells

miR‑145‑5p inhibits epithelial‑mesenchymal transition via the JNK signaling pathway by targeting MAP3K1 in non‑small cell lung cancer cells

All the “RAGE” in lung disease: The receptor for advanced glycation endproducts (RAGE) is a major mediator of pulmonary inflammatory responses

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