The Biology of Prostaglandins and Their Role as a Target for Allergic Airway Disease Therapy

Lee, Kijeong; Lee, Sang Hag; Kim, Tae Hoon

doi:10.3390/ijms21051851

Cited by 46 publications

(47 citation statements)

References 195 publications

(226 reference statements)

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“…The interactions between PGE2 and EP receptors depend on tissue and cell type, specific receptor expression, and differences in binding affinities, leading to unique patterns of EP receptor activation 30 . PGE2 can stimulate cAMP production through EP2 and EP4 receptors, whereas EP3 activation results in decreased cAMP synthesis and EP1 stimulation is coupled to Gq-activation and (enhanced) Ca 2+ signaling 27,30,31 . EP1 and EP3 receptors can mediate bronchoconstriction indirectly through activation of neural pathways 32 , as a consequence non-selective PGE2 analogues are unsuitable as pulmonary drugs.…”

Section: Discussionmentioning

confidence: 99%

A transcriptomics-guided drug target discovery strategy identifies novel receptor ligands for lung regeneration

Bos

Conlon

et al. 2021

Preprint

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Currently, there is no pharmacological treatment targeting defective tissue repair in chronic disease. Here we utilized a transcriptomics-guided drug target discovery strategy using gene signatures of smoking-associated chronic obstructive pulmonary disease (COPD) and from mice chronically exposed to cigarette smoke, identifying druggable targets expressed in alveolar epithelial progenitors of which we screened the function in lung organoids. We found several drug targets with regenerative potential of which EP and IP prostanoid receptor ligands had the most significant therapeutic potential in restoring cigarette smoke-induced defects in alveolar epithelial progenitors in vitro and in vivo. Mechanistically, we discovered by using scRNA-sequencing analysis that circadian clock and cell cycle/apoptosis signaling pathways were enriched in alveolar epithelial progenitor cells in COPD patients and in a relevant model of COPD, which was prevented by PGE2 or PGI2 mimetics. Conclusively, specific targeting of EP and IP receptors offers therapeutic potential for injury to repair in COPD.

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Section: Discussionmentioning

confidence: 99%

A transcriptomics-guided drug target discovery strategy identifies novel receptor ligands for lung regeneration

Bos

Conlon

et al. 2021

Preprint

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“…Cyclooxygenases ( COX), especially COX-2 isoform, play a pivotal role in the conversion of AA into different pro-inflammatory lipid mediators, including prostaglandins (PG) and thromboxanes ( 26 ). Despite the clear ligation of COX-2 activity with the development of the inflammatory response, it has also been proved that the inhibition of this enzyme impairs leukocyte clearance, indicating that some COX-2 derived mediators possess pro-resolving action.…”

Section: Spms Derived From Cyclooxygenasesmentioning

confidence: 99%

Could Arachidonic Acid-Derived Pro-Resolving Mediators Be a New Therapeutic Strategy for Asthma Therapy?

et al. 2020

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Asthma represents one of the leading chronic diseases worldwide and causes a high global burden of death and disability. In asthmatic patients, the exacerbation and chronification of the inflammatory response are often related to a failure in the resolution phase of inflammation. We reviewed the role of the main arachidonic acid (AA) specialized pro-resolving mediators (SPMs) in the resolution of chronic lung inflammation of asthmatics. AA is metabolized by two classes of enzymes, cyclooxygenases (COX), which produce prostaglandins (PGs) and thromboxanes, and lypoxygenases (LOX), which form leukotrienes and lipoxins (LXs). In asthma, two primary pro-resolving derived mediators from COXs are PGE2 and the cyclopentenone prostaglandin15-Deoxy-Delta-12,14-PGJ2 (15d-PGJ2) while from LOXs are the LXA4 and LXB4. In different models of asthma, PGE2, 15d-PGJ2, and LXs reduced lung inflammation and remodeling. Furthermore, these SPMs inhibited chemotaxis and function of several inflammatory cells involved in asthma pathogenesis, such as eosinophils, and presented an antiremodeling effect in airway epithelial, smooth muscle cells and fibroblasts in vitro. In addition, PGE2, 15d-PGJ2, and LXs are all able to induce macrophage reprogramming to an alternative M2 pro-resolving phenotype in vitro and in vivo. Although PGE2 and LXA4 showed some beneficial effects in asthmatic patients, there are limitations to their clinical use, since PGE2 caused side effects, while LXA4 presented low stability. Therefore, despite the strong evidence that these AA-derived SPMs induce resolution of both inflammatory response and tissue remodeling in asthma, safer and more stable analogs must be developed for further clinical investigation of their application in asthma treatment.

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“…PTGFR, also known as FP, belongs to the G protein-coupled receptor family of seven transmembranespanning receptors. PTGFR plays an important role in chondrocyte differentiation and cartilage development [26][27][28]. PGF2α exerts its biological activities by binding to its receptor, PTGFR [29].…”

Section: Discussionmentioning

confidence: 99%

Replicative Verification of Susceptibility Genes Previously Identified from Families with Segregating Developmental Dysplasia of the Hip

Wang²,

Chen

et al. 2020

Preprint

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Background: Developmental dysplasia of the hip (DDH) is a complex hip joint deformity with effects ranging from acetabulum malformation to irreversible hip dislocation. Previous studies suggest a significant association of four variations, Teneurin transmembrane protein 3 (TENM3) (chr4:183721398), Heparan sulfate proteoglycan 2 (HSPG2) (chr1:22201470), ATPase plasma membrane Ca2+ transporting 4 (ATP2B4) (chr1:203682345), and Prostaglandin F receptor (PTGFR) (chr1:79002214), with DDH susceptibility in families with segregating DDH. However, the association was not validated in sporadic cases and remains controversial. To confirm the association of the reported variations in these four genes with DDH, we conducted replicative verification in 250 sporadic samples with DDH from a Chinese Han population. Methods: We conducted Sanger sequencing after amplifying the variation sites. The results were compared with the reference sequence from the GRCh37 assembly in UCSC (http://genome.ucsc.edu). Results: Replication analysis of 250 sporadic samples by Sanger sequencing indicated that the four variations, TENM3 (chr4:183721398), HSPG2 (chr1:22201470), ATP2B4 (chr1:203682345), and PTGFR (chr1:79002214), were not associated with the susceptibility to DDH in the Chinese Han population.Conclusions: Further studies should be performed to identify other variations of these four genes that are potentially associated with DDH by whole-exome sequencing and the results should be verified in different populations.

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The Biology of Prostaglandins and Their Role as a Target for Allergic Airway Disease Therapy

Cited by 46 publications

References 195 publications

A transcriptomics-guided drug target discovery strategy identifies novel receptor ligands for lung regeneration

A transcriptomics-guided drug target discovery strategy identifies novel receptor ligands for lung regeneration

Could Arachidonic Acid-Derived Pro-Resolving Mediators Be a New Therapeutic Strategy for Asthma Therapy?

Replicative Verification of Susceptibility Genes Previously Identified from Families with Segregating Developmental Dysplasia of the Hip

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