Idiopathic pulmonary fibrosis (IPF), the most common form of idiopathic interstitial pneumonia, is a progressive, irreversible, and often fatal disease characterized by an abnormal fibrous response involving several areas of the lung. This study investigates whether sera from IPF patients could affect Human Pulmonary Microvascular Endothelial Cells (HPMECs) phenotype and functions and the molecular mechanisms underpinning these effects, which may be at the basis of IPF onset and progression. IPF sera markedly increased intracellular ROS levels in HPMECs, a phenomenon that was significantly counteracted by the broad-spectrum NOX inhibitor diphenyleneiodonium (DPI). Similarly, DPI was also able to significantly blunt IPF sera-elicited HPMECs proliferation. We next confirmed that IPF sera elicited EndMT in HPMECs and that NADPH-derived ROS mediated such a phenomenon. Results indeed show IPF sera were able to significantly decrease endothelial markers such as CDH5, CD3, vWF and increase mesenchymal markers including Col1, α-SMA. As the previous findings, such a phenomenon was also counteracted by DPI. Finally, we reported that the pleiotropic intracellular enzyme Protein Kinase C (PKC) may be the mediator of the ROS effect on HPMECs. In fact, the PCK inhibitor Chelerythrine (CHE) was able to significantly blunt the IPF-induced increase of ROS and proliferation. We propose that oxidant factors present in IPF may be at the base of disease-associated pathophysiology phenomena by eliciting a ROS-mediated HPMECs activation and phenotypic shift (intracellular ROS levels, cells proliferation, and EndMT). Our data demonstrate the presence of an IPF sera-induced EndMT, indicating this phenotypic shift as an important etiological mechanism in IPF-associated vascular damage and a potential therapeutic target for inhibiting obliterative vascular disorder and tissue fibrosis. Moreover, reduction of the IPF-related phenomena by DPI suggests antioxidants could be a potential therapeutic tool to prevent the progression of IPF-related complications including fibrosis

Idiopathic pulmonary fibrosis (IPF), the most common form of idiopathic interstitial pneumonia, is a progressive, irreversible, and often fatal disease characterized by an abnormal fibrous response involving several areas of the lung. This study investigates whether sera from IPF patients could affect Human Pulmonary Microvascular Endothelial Cells (HPMECs) phenotype and functions and the molecular mechanisms underpinning these effects, which may be at the basis of IPF onset and progression. IPF sera markedly increased intracellular ROS levels in HPMECs, a phenomenon that was significantly counteracted by the broad-spectrum NOX inhibitor diphenyleneiodonium (DPI). Similarly, DPI was also able to significantly blunt IPF sera-elicited HPMECs proliferation. We next confirmed that IPF sera elicited EndMT in HPMECs and that NADPH-derived ROS mediated such a phenomenon. Results indeed show IPF sera were able to significantly decrease endothelial markers such as CDH5, CD3, vWF and increase mesenchymal markers including Col1, α-SMA. As the previous findings, such a phenomenon was also counteracted by DPI. Finally, we reported that the pleiotropic intracellular enzyme Protein Kinase C (PKC) may be the mediator of the ROS effect on HPMECs. In fact, the PCK inhibitor Chelerythrine (CHE) was able to significantly blunt the IPF-induced increase of ROS and proliferation. We propose that oxidant factors present in IPF may be at the base of disease-associated pathophysiology phenomena by eliciting a ROS-mediated HPMECs activation and phenotypic shift (intracellular ROS levels, cells proliferation, and EndMT). Our data demonstrate the presence of an IPF sera-induced EndMT, indicating this phenotypic shift as an important etiological mechanism in IPF-associated vascular damage and a potential therapeutic target for inhibiting obliterative vascular disorder and tissue fibrosis. Moreover, reduction of the IPF-related phenomena by DPI suggests antioxidants could be a potential therapeutic tool to prevent the progression of IPF-related complications including fibrosis

ROLE OF ROS IN THE ENDOTHELIAL-TO-MESENCHYMAL TRANSITION INDUCED BY THE SERA FROM IDIOPATHIC PULMONARY FIBROSIS PATIENTS(2022 Apr 12).

ROLE OF ROS IN THE ENDOTHELIAL-TO-MESENCHYMAL TRANSITION INDUCED BY THE SERA FROM IDIOPATHIC PULMONARY FIBROSIS PATIENTS

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2022

Abstract

Idiopathic pulmonary fibrosis (IPF), the most common form of idiopathic interstitial pneumonia, is a progressive, irreversible, and often fatal disease characterized by an abnormal fibrous response involving several areas of the lung. This study investigates whether sera from IPF patients could affect Human Pulmonary Microvascular Endothelial Cells (HPMECs) phenotype and functions and the molecular mechanisms underpinning these effects, which may be at the basis of IPF onset and progression. IPF sera markedly increased intracellular ROS levels in HPMECs, a phenomenon that was significantly counteracted by the broad-spectrum NOX inhibitor diphenyleneiodonium (DPI). Similarly, DPI was also able to significantly blunt IPF sera-elicited HPMECs proliferation. We next confirmed that IPF sera elicited EndMT in HPMECs and that NADPH-derived ROS mediated such a phenomenon. Results indeed show IPF sera were able to significantly decrease endothelial markers such as CDH5, CD3, vWF and increase mesenchymal markers including Col1, α-SMA. As the previous findings, such a phenomenon was also counteracted by DPI. Finally, we reported that the pleiotropic intracellular enzyme Protein Kinase C (PKC) may be the mediator of the ROS effect on HPMECs. In fact, the PCK inhibitor Chelerythrine (CHE) was able to significantly blunt the IPF-induced increase of ROS and proliferation. We propose that oxidant factors present in IPF may be at the base of disease-associated pathophysiology phenomena by eliciting a ROS-mediated HPMECs activation and phenotypic shift (intracellular ROS levels, cells proliferation, and EndMT). Our data demonstrate the presence of an IPF sera-induced EndMT, indicating this phenotypic shift as an important etiological mechanism in IPF-associated vascular damage and a potential therapeutic target for inhibiting obliterative vascular disorder and tissue fibrosis. Moreover, reduction of the IPF-related phenomena by DPI suggests antioxidants could be a potential therapeutic tool to prevent the progression of IPF-related complications including fibrosis
Idiopathic pulmonary fibrosis (IPF), the most common form of idiopathic interstitial pneumonia, is a progressive, irreversible, and often fatal disease characterized by an abnormal fibrous response involving several areas of the lung. This study investigates whether sera from IPF patients could affect Human Pulmonary Microvascular Endothelial Cells (HPMECs) phenotype and functions and the molecular mechanisms underpinning these effects, which may be at the basis of IPF onset and progression. IPF sera markedly increased intracellular ROS levels in HPMECs, a phenomenon that was significantly counteracted by the broad-spectrum NOX inhibitor diphenyleneiodonium (DPI). Similarly, DPI was also able to significantly blunt IPF sera-elicited HPMECs proliferation. We next confirmed that IPF sera elicited EndMT in HPMECs and that NADPH-derived ROS mediated such a phenomenon. Results indeed show IPF sera were able to significantly decrease endothelial markers such as CDH5, CD3, vWF and increase mesenchymal markers including Col1, α-SMA. As the previous findings, such a phenomenon was also counteracted by DPI. Finally, we reported that the pleiotropic intracellular enzyme Protein Kinase C (PKC) may be the mediator of the ROS effect on HPMECs. In fact, the PCK inhibitor Chelerythrine (CHE) was able to significantly blunt the IPF-induced increase of ROS and proliferation. We propose that oxidant factors present in IPF may be at the base of disease-associated pathophysiology phenomena by eliciting a ROS-mediated HPMECs activation and phenotypic shift (intracellular ROS levels, cells proliferation, and EndMT). Our data demonstrate the presence of an IPF sera-induced EndMT, indicating this phenotypic shift as an important etiological mechanism in IPF-associated vascular damage and a potential therapeutic target for inhibiting obliterative vascular disorder and tissue fibrosis. Moreover, reduction of the IPF-related phenomena by DPI suggests antioxidants could be a potential therapeutic tool to prevent the progression of IPF-related complications including fibrosis
fibrosis; HPMECs; DPI; EndMT; ROS
ROS
PHAN, THI HANG GIANG
ROLE OF ROS IN THE ENDOTHELIAL-TO-MESENCHYMAL TRANSITION INDUCED BY THE SERA FROM IDIOPATHIC PULMONARY FIBROSIS PATIENTS(2022 Apr 12).
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11388/294528
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