Dopamine receptor agonists ameliorate bleomycin-induced pulmonary fibrosis by repressing fibroblast differentiation and proliferation

Mou, Yong; Liu, Juan; Pan, Ting; Wang, Qi; Miao, Kang; Xu, Yongjian; Xiong, Weining; Yu, Jun

doi:10.1016/j.biopha.2021.111500

Cited by 9 publications

(3 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, we demonstrated that treatment with a D3R agonist prevented morphine-induced cardiac fibrosis ( 18 ). Recently, D1R was reported to be upregulated in lung myofibroblasts of patients with idiopathic pulmonary fibrosis ( 19 ). Together, these data indicate a role for D1R and D3R in cardiac fibrosis.…”

Section: Introductionmentioning

confidence: 99%

Loss of Function in Dopamine D3 Receptor Attenuates Left Ventricular Cardiac Fibroblast Migration and Proliferation in vitro

Kisling

Byrne

Parekh

et al. 2021

Front. Cardiovasc. Med.

View full text Add to dashboard Cite

Evidence suggests the existence of an intracardiac dopaminergic system that plays a pivotal role in regulating cardiac function and fibrosis through G-protein coupled receptors, particularly mediated by dopamine receptor 3 (D3R). However, the expression of dopamine receptors in cardiac tissue and their role in cardiac fibroblast function is unclear. In this brief report, first we determined expression of D1R and D3R both in left ventricle (LV) tissue and fibroblasts. Then, we explored the role of D3R in the proliferation and migration of fibroblast cell cultures using both genetic and pharmaceutical approaches; specifically, we compared cardiac fibroblasts isolated from LV of wild type (WT) and D3R knockout (D3KO) mice in response to D3R-specific pharmacological agents. Finally, we determined if loss of D3R function could significantly alter LV fibroblast expression of collagen types I (Col1a1) and III (Col3a1). Cardiac fibroblast proliferation was attenuated in D3KO cells, mimicking the behavior of WT cardiac fibroblasts treated with D3R antagonist. In response to scratch injury, WT cardiac fibroblasts treated with the D3R agonist, pramipexole, displayed enhanced migration compared to control WT and D3KO cells. Loss of function in D3R resulted in attenuation of both proliferation and migration in response to scratch injury, and significantly increased the expression of Col3a1 in LV fibroblasts. These findings suggest that D3R may mediate cardiac fibroblast function during the wound healing response. To our knowledge this is the first report of D3R's expression and functional significance directly in mouse cardiac fibroblasts.

show abstract

Section: Introductionmentioning

confidence: 99%

Loss of Function in Dopamine D3 Receptor Attenuates Left Ventricular Cardiac Fibroblast Migration and Proliferation in vitro

Kisling

Byrne

Parekh

et al. 2021

Front. Cardiovasc. Med.

View full text Add to dashboard Cite

show abstract

“… 24 In addition, human normal lung fibroblast cell lines have also been used for pulmonary fibrosis studies, such as WI-38 cells, IMR-90 cells, and normal human lung fibroblast (NHLF) cells. 25 – 27 WI-38 cells and IMR-90 cells were incubated in DMEM medium, while NHLF cells were incubated in FGM™-2 fibroblasts growth medium-2 BulletKit.…”

Section: Present Research Methodology For Ipfmentioning

confidence: 99%

Exploring therapeutic targets for molecular therapy of idiopathic pulmonary fibrosis

Li,

Jiang,

Zhu

et al. 2024

Science Progress

View full text Add to dashboard Cite

Idiopathic pulmonary fibrosis is a chronic and progressive interstitial lung disease with a poor prognosis. Idiopathic pulmonary fibrosis is characterized by repeated alveolar epithelial damage leading to abnormal repair. The intercellular microenvironment is disturbed, leading to continuous activation of fibroblasts and myofibroblasts, deposition of extracellular matrix, and ultimately fibrosis. Moreover, pulmonary fibrosis was also found as a COVID-19 complication. Currently, two drugs, pirfenidone and nintedanib, are approved for clinical therapy worldwide. However, they can merely slow the disease's progression rather than rescue it. These two drugs have other limitations, such as lack of efficacy, adverse effects, and poor pharmacokinetics. Consequently, a growing number of molecular therapies have been actively developed. Treatment options for IPF are becoming increasingly available. This article reviews the research platform, including cell and animal models involved in molecular therapy studies of idiopathic pulmonary fibrosis as well as the promising therapeutic targets and their development progress during clinical trials. The former includes patient case/control studies, cell models, and animal models. The latter includes transforming growth factor-beta, vascular endothelial growth factor, platelet-derived growth factor, fibroblast growth factor, lysophosphatidic acid, interleukin-13, Rho-associated coiled-coil forming protein kinase family, and Janus kinases/signal transducers and activators of transcription pathway. We mainly focused on the therapeutic targets that have not only entered clinical trials but were publicly published with their clinical outcomes. Moreover, this work provides an outlook on some promising targets for further validation of their possibilities to cure the disease.

show abstract

“…Having confirmed the anti-lung cancer potential of E5, we next evaluated its therapeutical effect for IPF which features pathological findings including fibroblast migration, proliferation, epithelial mesenchymal transition (EMT) [37][38] . Initially, we assessed the anti-fibrosis ability of E5 in vitro using IMR-90 cell line 38 induced by transforming growth factor β1 (TGF-β1), a crucial profibrotic factor in lung fibrosis which can enhance the expression of fibrosis marker α-SMA.…”

Section: Anti-idiopathic Pulmonary Fibrosis Study In Vitro and In Vivomentioning

confidence: 99%

N-Phenyl-2-Pyridone-Derived Endoperoxide Exhibiting Dual Activity by Suppressing both Lung Cancer and Idiopathic Pulmonary Fibrosis

Wang,

Wu,

Liu

et al. 2024

Preprint

View full text Add to dashboard Cite

Conventional light-driven photodynamic therapy (PDT) to generate toxic singlet oxygen are potential for cancer therapeutics but limited by the light penetrability and hypoxia tumor. PDT-involved combinational therapy could enhance overall therapeutic effects and reduce drug resistance, while disadvantages such as diverse pharmacokinetics among different ingredients, low active-ingredient loading, inevitably utilization of non-functional components need to be addressed. Here we report an endoperoxide E5 synthesized via ‘in vitro’ PDT could spontaneously deliver singlet oxygen, triplet oxygen and 3-methyl-N-phenyl-2-pyridone as an analogue of pirfenidone (Approved drug for treatment of idiopathic pulmonary fibrosis), showing great potential for treating non-small cell lung cancer and idiopathic pulmonary fibrosis. In aqueous solution, E5 could undergo a clear cycloreversion to afford three components with a half-life time of 8.3 hours and it efficiently suppress the migration and invasion of lung cancer cell as well as the TGF-b1 induced fibrosis in vitro. In vivo experiments suggest that E5 not only efficiently inhibits tumor growth, decreases the HIF-1α protein levels, relieves idiopathic pulmonary fibrosis, but shows good biocompatibility. Many evidence reveal that both singlet oxygen and 3-methyl-N-phenyl-2-pyridone are therapeutic ingredients, and triplet oxygen could relieve tumor hypoxia which is an inevitable issue in conventional PDT. Our study validates that endoperoxides as single active components containing multiple ingredients including singlet oxygen are of exceptionally therapeutic potential.

show abstract

Dopamine receptor agonists ameliorate bleomycin-induced pulmonary fibrosis by repressing fibroblast differentiation and proliferation

Cited by 9 publications

References 42 publications

Loss of Function in Dopamine D3 Receptor Attenuates Left Ventricular Cardiac Fibroblast Migration and Proliferation in vitro

Loss of Function in Dopamine D3 Receptor Attenuates Left Ventricular Cardiac Fibroblast Migration and Proliferation in vitro

Exploring therapeutic targets for molecular therapy of idiopathic pulmonary fibrosis

N-Phenyl-2-Pyridone-Derived Endoperoxide Exhibiting Dual Activity by Suppressing both Lung Cancer and Idiopathic Pulmonary Fibrosis

Contact Info

Product

Resources

About