Aberrant Expression of ACO1 in Vasculatures Parallels Progression of Idiopathic Pulmonary Fibrosis
Rationale: Idiopathic pulmonary fibrosis (IPF) is characterized by mitochondrial dysfunction. However, details about the non-mitochondrial enzymes that sustain the proliferative nature of IPF are unclear. Aconitases are a family of enzymes that sustain metabolism inside and outside mitochondria. It...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-07-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.890380/full |
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| author | Jutaro Fukumoto Muling Lin Mudassir Meraj Banday Sahebgowda Sidramagowda Patil Sudarshan Krishnamurthy Mason Breitzig Ramani Soundararajan Lakshmi Galam Venkata Ramireddy Narala Venkata Ramireddy Narala Colleen Johns Kapilkumar Patel Kapilkumar Patel John Dunning Richard F. Lockey Nirmal S. Sharma Narasaiah Kolliputi Narasaiah Kolliputi |
| author_facet | Jutaro Fukumoto Muling Lin Mudassir Meraj Banday Sahebgowda Sidramagowda Patil Sudarshan Krishnamurthy Mason Breitzig Ramani Soundararajan Lakshmi Galam Venkata Ramireddy Narala Venkata Ramireddy Narala Colleen Johns Kapilkumar Patel Kapilkumar Patel John Dunning Richard F. Lockey Nirmal S. Sharma Narasaiah Kolliputi Narasaiah Kolliputi |
| author_sort | Jutaro Fukumoto |
| collection | DOAJ |
| description | Rationale: Idiopathic pulmonary fibrosis (IPF) is characterized by mitochondrial dysfunction. However, details about the non-mitochondrial enzymes that sustain the proliferative nature of IPF are unclear. Aconitases are a family of enzymes that sustain metabolism inside and outside mitochondria. It is hypothesized that aconitase 1 (ACO1) plays an important role in the pathogenesis of IPF given that ACO1 represents an important metabolic hub in the cytoplasm.Objectives: To determine if ACO1 expression in IPF lungs shows specific patterns that may be important in the pathogenesis of IPF. To determine the similarities and differences in ACO1 expression in IPF, bleomycin-treated, and aging lungs.Methods: ACO1 expression in IPF lungs were characterized and compared to non-IPF controls by western blotting, immunostaining, and enzymatic activity assay. ACO1-expressing cell types were identified by multicolor immunostaining. Using similar methods, the expression profiles of ACO1 in IPF lungs versus bleomycin-treated and aged mice were investigated.Measurements and main results: Lower lobes of IPF lungs, unlike non-IPF controls, exhibit significantly high levels of ACO1. Most of the signals colocalize with von Willebrand factor (vWF), a lineage marker for vascular endothelial cells. Bleomycin-treated lungs also show high ACO1 expressions. However, most of the signals colocalize with E-cadherin and/or prosurfactant protein C, representative epithelial cell markers, in remodeled areas.Conclusions: A characteristic ACO1 expression profile observed in IPF vasculatures may be a promising diagnostic target. It also may give clues as to how de novo angiogenesis contributes to the irreversible nature of IPF. |
| first_indexed | 2024-04-13T05:00:46Z |
| format | Article |
| id | doaj.art-8d76ad8838d241ecaf18d06e8a420def |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-13T05:00:46Z |
| publishDate | 2022-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-8d76ad8838d241ecaf18d06e8a420def2022-12-22T03:01:21ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-07-011310.3389/fphar.2022.890380890380Aberrant Expression of ACO1 in Vasculatures Parallels Progression of Idiopathic Pulmonary FibrosisJutaro Fukumoto0Muling Lin1Mudassir Meraj Banday2Sahebgowda Sidramagowda Patil3Sudarshan Krishnamurthy4Mason Breitzig5Ramani Soundararajan6Lakshmi Galam7Venkata Ramireddy Narala8Venkata Ramireddy Narala9Colleen Johns10Kapilkumar Patel11Kapilkumar Patel12John Dunning13Richard F. Lockey14Nirmal S. Sharma15Narasaiah Kolliputi16Narasaiah Kolliputi17Division of Allergy and Immunology, Department of Internal Medicine, University of South Florida, Tampa, FL, United StatesDivision of Allergy and Immunology, Department of Internal Medicine, University of South Florida, Tampa, FL, United StatesPulmonary and Critical Care Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, United StatesDivision of Allergy and Immunology, Department of Internal Medicine, University of South Florida, Tampa, FL, United StatesDivision of Allergy and Immunology, Department of Internal Medicine, University of South Florida, Tampa, FL, United StatesDivision of Allergy and Immunology, Department of Internal Medicine, University of South Florida, Tampa, FL, United StatesDivision of Allergy and Immunology, Department of Internal Medicine, University of South Florida, Tampa, FL, United StatesDivision of Allergy and Immunology, Department of Internal Medicine, University of South Florida, Tampa, FL, United StatesDivision of Allergy and Immunology, Department of Internal Medicine, University of South Florida, Tampa, FL, United StatesDepartment of Zoology, Yogi Vemana University, Kadapa, IndiaDivision of Allergy and Immunology, Department of Internal Medicine, University of South Florida, Tampa, FL, United StatesPulmonary, Critical Care & Sleep Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL, United StatesAdvanced Lung Diseases & Lung Transplantation, Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL, United StatesDivision of Cardiothoracic Surgery, Department of Surgery, University of South Florida, Tampa, FL, United StatesDivision of Allergy and Immunology, Department of Internal Medicine, University of South Florida, Tampa, FL, United StatesPulmonary and Critical Care Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, United StatesDivision of Allergy and Immunology, Department of Internal Medicine, University of South Florida, Tampa, FL, United StatesDepartment of Molecular Medicine, University of South Florida, Tampa, FL, United StatesRationale: Idiopathic pulmonary fibrosis (IPF) is characterized by mitochondrial dysfunction. However, details about the non-mitochondrial enzymes that sustain the proliferative nature of IPF are unclear. Aconitases are a family of enzymes that sustain metabolism inside and outside mitochondria. It is hypothesized that aconitase 1 (ACO1) plays an important role in the pathogenesis of IPF given that ACO1 represents an important metabolic hub in the cytoplasm.Objectives: To determine if ACO1 expression in IPF lungs shows specific patterns that may be important in the pathogenesis of IPF. To determine the similarities and differences in ACO1 expression in IPF, bleomycin-treated, and aging lungs.Methods: ACO1 expression in IPF lungs were characterized and compared to non-IPF controls by western blotting, immunostaining, and enzymatic activity assay. ACO1-expressing cell types were identified by multicolor immunostaining. Using similar methods, the expression profiles of ACO1 in IPF lungs versus bleomycin-treated and aged mice were investigated.Measurements and main results: Lower lobes of IPF lungs, unlike non-IPF controls, exhibit significantly high levels of ACO1. Most of the signals colocalize with von Willebrand factor (vWF), a lineage marker for vascular endothelial cells. Bleomycin-treated lungs also show high ACO1 expressions. However, most of the signals colocalize with E-cadherin and/or prosurfactant protein C, representative epithelial cell markers, in remodeled areas.Conclusions: A characteristic ACO1 expression profile observed in IPF vasculatures may be a promising diagnostic target. It also may give clues as to how de novo angiogenesis contributes to the irreversible nature of IPF.https://www.frontiersin.org/articles/10.3389/fphar.2022.890380/fulllung injuryACO1IRP1IPFangiogenesis |
| spellingShingle | Jutaro Fukumoto Muling Lin Mudassir Meraj Banday Sahebgowda Sidramagowda Patil Sudarshan Krishnamurthy Mason Breitzig Ramani Soundararajan Lakshmi Galam Venkata Ramireddy Narala Venkata Ramireddy Narala Colleen Johns Kapilkumar Patel Kapilkumar Patel John Dunning Richard F. Lockey Nirmal S. Sharma Narasaiah Kolliputi Narasaiah Kolliputi Aberrant Expression of ACO1 in Vasculatures Parallels Progression of Idiopathic Pulmonary Fibrosis Frontiers in Pharmacology lung injury ACO1 IRP1 IPF angiogenesis |
| title | Aberrant Expression of ACO1 in Vasculatures Parallels Progression of Idiopathic Pulmonary Fibrosis |
| title_full | Aberrant Expression of ACO1 in Vasculatures Parallels Progression of Idiopathic Pulmonary Fibrosis |
| title_fullStr | Aberrant Expression of ACO1 in Vasculatures Parallels Progression of Idiopathic Pulmonary Fibrosis |
| title_full_unstemmed | Aberrant Expression of ACO1 in Vasculatures Parallels Progression of Idiopathic Pulmonary Fibrosis |
| title_short | Aberrant Expression of ACO1 in Vasculatures Parallels Progression of Idiopathic Pulmonary Fibrosis |
| title_sort | aberrant expression of aco1 in vasculatures parallels progression of idiopathic pulmonary fibrosis |
| topic | lung injury ACO1 IRP1 IPF angiogenesis |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.890380/full |
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