The role of free fatty acids in idiopathic pulmonary fibrosis

Kim, Haksu; Lee, Kwang Min; Song, Ha Eun; Choi, Kwang Hun; Hwang, Jung Jin; Yoo, Hyun Ju; Song, Jin Woo

doi:10.1183/1393003.congress-2017.oa4635

Cited by 6 publications

(6 citation statements)

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“…Mechanistically, we show for the first time that AZGP1 has regulatory functions in kidney lipid metabolism. The importance of balanced fatty acid degradation in the development of fibrosis has been shown in different organs like the lung, liver, and kidney [ 16 , 22 , 23 , 24 ]. In tubular epithelial cells, lipid accumulation and defective FAO have been recognized as key mechanisms in promoting kidney fibrosis [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

The Therapeutic Potential of Zinc-Alpha2-Glycoprotein (AZGP1) in Fibrotic Kidney Disease

Sörensen-Zender

Rong

Haller

et al. 2022

IJMS

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Chronic kidney disease (CKD) is characterized by a long-term loss of kidney function and, in most cases, by progressive fibrosis. Zinc-alpha2-glycoprotein (AZGP1) is a secreted protein, which is expressed in many different tissues and has been associated with a variety of functions. In a previous study, we have shown in cell culture and in AZGP1 deficient mice that AZGP1 has protective anti-fibrotic effects. In the present study, we tested the therapeutic potential of an experimental increase in AZGP1 using two different strategies. (1) C57Bl/6J mice were treated systemically with recombinant AZGP1, and (2) a transgenic mouse strain was generated to overexpress AZGP1 conditionally in proximal tubular cells. Mice underwent unilateral uretic obstruction as a pro-fibrotic kidney stress model, and kidneys were examined after 14 days. Recombinant AZGP1 treatment was accompanied by better preservation of tubular integrity, reduced collagen deposition, and lower expression of injury and fibrosis markers. Weaker but similar tendencies were observed in transgenic AZGP1 overexpressing mice. Higher AZGP1 levels led to a significant reduction in stress-induced accumulation of tubular lipid droplets, which was paralleled by improved expression of key players in lipid metabolism and fatty acid oxidation. Together these data show beneficial effects of elevated AZGP1 levels in fibrotic kidney disease and highlight a novel link to tubular cell lipid metabolism, which might open up new opportunities for CKD treatment.

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Section: Discussionmentioning

confidence: 99%

The Therapeutic Potential of Zinc-Alpha2-Glycoprotein (AZGP1) in Fibrotic Kidney Disease

Sörensen-Zender

Rong

Haller

et al. 2022

IJMS

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“…Although palmitic and stearic acids may play a differential role in pulmonary disease pathogenesis, increased circulating stearic acid has been shown to cause cardiac and pancreatic β cell lipotoxicity. [39][40][41] We have demonstrated that brominated fatty aldehyde, when administered into the LV, can cause cardiac damage and dysfunction similar to Br 2 inhalation; however, the effects of elevated BFAs need to be investigated. 2 Pulmonary damage as assessed by measuring BALF protein, which is indicative of alveolar-capillary disruption in the lung, correlated with total bromostearic acid contents in cardiopulmonary tissue and plasma.…”

Section: Discussionmentioning

confidence: 99%

Circulating and tissue biomarkers as predictors of bromine gas inhalation

Juncos

Shakil

Ahmad

et al. 2020

Annals of the New York Academy of Sciences

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The threat from deliberate or accidental exposure to halogen gases is increasing, as is their industrial applications and use as chemical warfare agents. Biomarkers that can identify halogen exposure, diagnose victims of exposure or predict injury severity, and enable appropriate treatment are lacking. We conducted these studies to determine and validate biomarkers of bromine (Br 2) toxicity and correlate the symptoms and the extent of cardiopulmonary injuries. Unanesthetized rats were exposed to Br 2 and monitored noninvasively for clinical scores and pulse oximetry. Animals were euthanized and grouped at various time intervals to assess brominated fatty acid (BFA) content in the plasma, lung, and heart using mass spectrometry. Bronchoalveolar lavage fluid (BALF) protein content was used to assess pulmonary injury. Cardiac troponin I (cTnI) was assessed in the plasma to evaluate cardiac injury. The blood, lung, and cardiac tissue BFA content significantly correlated with the clinical scores, tissue oxygenation, heart rate, and cardiopulmonary injury parameters. Total (free + esterified) bromostearic acid levels correlated with lung injury, as indicated by BALF protein content, and free bromostearic acid levels correlated with plasma cTnI levels. Thus, BFAs and cardiac injury biomarkers can identify Br 2 exposure and predict the severity of organ damage.

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“…Apart from lipid and fatty acids, lipid mediators are also involved in the pathogenesis of IPF by regulating the exhibition of pro- and anti-fibrotic effects in IPF. Lipid mediators are a class of bioactive lipids that are derived from phospholipids, sphingolipids, and polyunsaturated fatty acids and can be divided into pro-inflammatory/anti-fibrotic lipid mediators (such as prostaglandins and leukotrienes) and specialized pro-resolving/pro-fibrotic lipid mediators (SPMs) (including lipoxins, resolvins, maresins, and protectins) [ 160 ]. Regardless of the cell types involved, lipid mediators play roles in the activation of myofibroblasts, the deposition of ECM, and the remodeling of lung architecture and fibrosis [ 161 ].…”

Section: Ctgf Drives Senescence In Ipfmentioning

confidence: 99%

Connective Tissue Growth Factor in Idiopathic Pulmonary Fibrosis: Breaking the Bridge

Effendi

Nagano

2022

IJMS

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CTGF is upregulated in patients with idiopathic pulmonary fibrosis (IPF), characterized by the deposition of a pathological extracellular matrix (ECM). Additionally, many omics studies confirmed that aberrant cellular senescence-associated mitochondria dysfunction and metabolic reprogramming had been identified in different IPF lung cells (alveolar epithelial cells, alveolar endothelial cells, fibroblasts, and macrophages). Here, we reviewed the role of the CTGF in IPF lung cells to mediate anomalous senescence-related metabolic mechanisms that support the fibrotic environment in IPF.

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The role of free fatty acids in idiopathic pulmonary fibrosis

Cited by 6 publications

References 0 publications

The Therapeutic Potential of Zinc-Alpha2-Glycoprotein (AZGP1) in Fibrotic Kidney Disease

The Therapeutic Potential of Zinc-Alpha2-Glycoprotein (AZGP1) in Fibrotic Kidney Disease

Circulating and tissue biomarkers as predictors of bromine gas inhalation

Connective Tissue Growth Factor in Idiopathic Pulmonary Fibrosis: Breaking the Bridge

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