Dysregulated expression of hypoxia-inducible factors augments myofibroblasts differentiation in idiopathic pulmonary fibrosis

Aquino‐Gálvez, Arnoldo; González-Ávila, Georgina; Jiménez-Sánchez, Laura; Maldonado-Martínez, Héctor Aquiles; Cisneros, José; Toscano-Marquez, Fernanda; Castillejos-López, Manuel; Torres‐Espíndola, Luz María; Velázquez‐Cruz, Rafael; Rodríguez, Víctor Hugo Olivera; Flores‐Soto, Edgar; Solís‐Chagoyán, Héctor; Cabello, Carlos; Zúñiga, Joaquı́n; Romero, Yair

doi:10.1186/s12931-019-1100-4

Cited by 46 publications

(32 citation statements)

References 35 publications

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“…5). [281][282][283][284]. These include the augmented expression of myofibroblast differentiation markers, such as αSMA and β-actin, in response to increased levels of HIF-1α and HIF-2α in human normal fibroblasts exposed to hypoxic conditions and in lung tissue from IPF patients [284].…”

Section: Hypoxiamentioning

confidence: 99%

“…These include the augmented expression of myofibroblast differentiation markers, such as αSMA and β-actin, in response to increased levels of HIF-1α and HIF-2α in human normal fibroblasts exposed to hypoxic conditions and in lung tissue from IPF patients [ 284 ]. Noteworthy, in the same model, HIF-3α expression was decreased, probably as consequence of its hypermethylation, which negatively regulates the hypoxia signaling pathway [ 284 , 285 ]. In a mice model of bleomycin-induced fibrosis, HIF-1α knockout reduced lung fibrosis and alveolar epithelial cells proliferation [ 283 ].…”

Section: Cellular and Molecular Mechanisms In Ipfmentioning

confidence: 99%

See 1 more Smart Citation

Emerging cellular and molecular determinants of idiopathic pulmonary fibrosis

Phan

Paliogiannis

Nasrallah

et al. 2020

Cell. Mol. Life Sci.

238

152

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Idiopathic pulmonary fibrosis (IPF), the most common form of idiopathic interstitial pneumonia, is a progressive, irreversible, and typically lethal disease characterized by an abnormal fibrotic response involving vast areas of the lungs. Given the poor knowledge of the mechanisms underpinning IPF onset and progression, a better understanding of the cellular processes and molecular pathways involved is essential for the development of effective therapies, currently lacking. Besides a number of established IPF-associated risk factors, such as cigarette smoking, environmental factors, comorbidities, and viral infections, several other processes have been linked with this devastating disease. Apoptosis, senescence, epithelial-mesenchymal transition, endothelial-mesenchymal transition, and epithelial cell migration have been shown to play a key role in IPF-associated tissue remodeling. Moreover, molecules, such as chemokines, cytokines, growth factors, adenosine, glycosaminoglycans, non-coding RNAs, and cellular processes including oxidative stress, mitochondrial dysfunction, endoplasmic reticulum stress, hypoxia, and alternative polyadenylation have been linked with IPF development. Importantly, strategies targeting these processes have been investigated to modulate abnormal cellular phenotypes and maintain tissue homeostasis in the lung. This review provides an update regarding the emerging cellular and molecular mechanisms involved in the onset and progression of IPF.

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Section: Hypoxiamentioning

confidence: 99%

Section: Cellular and Molecular Mechanisms In Ipfmentioning

confidence: 99%

Emerging cellular and molecular determinants of idiopathic pulmonary fibrosis

Phan

Paliogiannis

Nasrallah

et al. 2020

Cell. Mol. Life Sci.

238

152

View full text Add to dashboard Cite

show abstract

“…IPF patients suffer from an impaired pulmonary gas exchange and chronic arterial hypoxemia ( 89 ). The important role of hypoxia and HIFs on fibroblast proliferation and differentiation has been studied extensively ( 90 – 92 ). Besides the direct impact on fibroblasts, hypoxia is regarded as one of the potent stimuli for the production of proinflammatory cytokines.…”

Section: Hypoxia and Inflammation In Lung Injurymentioning

confidence: 99%

Adenosine at the Interphase of Hypoxia and Inflammation in Lung Injury

Berg

Mills

et al. 2021

Front. Immunol.

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Hypoxia and inflammation often coincide in pathogenic conditions such as acute respiratory distress syndrome (ARDS) and chronic lung diseases, which are significant contributors to morbidity and mortality for the general population. For example, the recent global outbreak of Coronavirus disease 2019 (COVID-19) has placed viral infection-induced ARDS under the spotlight. Moreover, chronic lung disease ranks the third leading cause of death in the United States. Hypoxia signaling plays a diverse role in both acute and chronic lung inflammation, which could partially be explained by the divergent function of downstream target pathways such as adenosine signaling. Particularly, hypoxia signaling activates adenosine signaling to inhibit the inflammatory response in ARDS, while in chronic lung diseases, it promotes inflammation and tissue injury. In this review, we discuss the role of adenosine at the interphase of hypoxia and inflammation in ARDS and chronic lung diseases, as well as the current strategy for therapeutic targeting of the adenosine signaling pathway.

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“…An extensive and unbiased study of the influence of HBO exposure on lung tissue is required, not only to validate the safety of this therapy, but also to potentially expand diseases which this treatment can be used for, such as those where hypoxia drives the pathogenesis of the disease [19][20][21][22][23]. Using CIBERSORTx deconvolution of RNA-seq in mice lungs exposed to HBO, we identify changes in several mesenchymal cell subtypes.…”

Section: Introductionmentioning

confidence: 99%

Deconvolution of RNA-Seq Analysis of Hyperbaric Oxygen-Treated Mice Lungs Reveals Mesenchymal Cell Subtype Changes

Yuan

Zhou

et al. 2020

IJMS

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Hyperbaric oxygen (HBO) is widely applied to treat several hypoxia-related diseases. Previous studies have focused on the immediate effect of HBO-exposure induced oxidative stress on the lungs, but knowledge regarding the chronic effects from repetitive HBO exposure is limited, especially at the gene expression level. We found that repetitive HBO exposure did not alter the morphology of murine lungs. However, by deconvolution of RNA-seq from those mice lungs using CIBERSORTx and the expression profile matrices of 8 mesenchymal cell subtypes obtained from bleomycin-treated mouse lungs, we identify several mesenchymal cell subtype changes. These include increases in Col13a1 matrix fibroblasts, mesenchymal progenitors and mesothelial cell populations and decreases in lipofibroblasts, endothelial and Pdgfrb high cell populations. Our data suggest that repetitive HBO exposure may affect biological processes in the lungs such as response to wounding, extracellular matrix, vasculature development and immune response.

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Dysregulated expression of hypoxia-inducible factors augments myofibroblasts differentiation in idiopathic pulmonary fibrosis

Cited by 46 publications

References 35 publications

Emerging cellular and molecular determinants of idiopathic pulmonary fibrosis

Emerging cellular and molecular determinants of idiopathic pulmonary fibrosis

Adenosine at the Interphase of Hypoxia and Inflammation in Lung Injury

Deconvolution of RNA-Seq Analysis of Hyperbaric Oxygen-Treated Mice Lungs Reveals Mesenchymal Cell Subtype Changes

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