Hypoxia-Induced Mitogenic Factor: A Multifunctional Protein Involved in Health and Disease

Lv, Moyang; Liu, Wenjuan

doi:10.3389/fcell.2021.691774

Cited by 7 publications

(8 citation statements)

References 55 publications

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“…The Retnla gene in mice encodes resistin‐like molecule alpha (RETNLA or RELMα), also known as found in inflammatory zone 1 (FIZZ1) and hypoxia‐induced mitogenic factor (HIMF). Recently it was reported to be involved in several pathological processes, including angiogenesis, vasoconstriction, inflammation and fibrosis and implicated in pulmonary, cardiovascular and metabolic diseases (Lv & Liu, 2021 ; Lin & Johns, 2020 ; Kumar et al, 2018 ). With regards to the cardiovascular system, HIMF may, for instance, play a critical role in the development of cardiomyocyte hypertrophy and pulmonary hypertension via hypoxia‐induced factor‐1 α (HIF‐1 α) mechanisms (Kumar et al, 2018 ; Johns et al, 2016 ) or pulmonary hypertension through phosphatidylinositol 3‐kinase (PI3K) pathways (Teng et al, 2003 ), and targeting HIMF may represent a potential therapeutic strategy (Kumar et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

Identification of exercise‐regulated genes in mice exposed to cigarette smoke

Aakerøy

Cheng

Sustova

et al. 2022

Physiological Reports

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Cigarette smoke (CS) is the major risk factor for COPD and is linked to cardiopulmonary dysfunction. Exercise training as part of pulmonary rehabilitation is recommended for all COPD patients. It has several physiological benefits, but the mechanisms involved remain poorly defined. Here, we employed transcriptomic profiling and examined lung endothelium to investigate novel interactions between exercise and CS on cardiopulmonary alterations. Mice were exposed to 20 weeks of CS, CS + 6 weeks of high‐intensity interval training on a treadmill, or control. Lung and cardiac (left and right ventricle) tissue were harvested and RNA‐sequencing was performed and validated with RT‐qPCR. Immunohistochemistry assessed pulmonary arteriolar changes. Transcriptome analysis between groups revealed 37 significantly regulated genes in the lung, 21 genes in the left ventricle, and 43 genes in the right ventricle (likelihood‐ratio test). Validated genes that showed interaction between exercise and CS included angiotensinogen ( p = 0.002) and resistin‐like alpha ( p = 0.019) in left ventricle, with prostacyclin synthetase different in pulmonary arterioles ( p = 0.004). Transcriptomic profiling revealed changes in pulmonary and cardiac tissue following exposure to CS, with exercise training exerting rescue effects. Exercise‐regulated genes included angiotensinogen and resistin‐like alpha, however, it remains unclear if these represent potential candidate genes or biomarkers that could play a role during pulmonary rehabilitation.

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Section: Discussionmentioning

confidence: 99%

Identification of exercise‐regulated genes in mice exposed to cigarette smoke

Aakerøy

Cheng

Sustova

et al. 2022

Physiological Reports

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“…HIMF strongly activated Akt phosphorylation. It promotes SMC proliferation through the PI3K/Akt pathway ( Figure 4 ) [ 122 ]. HIMF increases vascular pressure and vascular resistance more potently than either ET-1 or Ang II.…”

Section: Transcription Factors Are Involved In Hypoxia-induced Vascul...mentioning

confidence: 99%

Mechanism of Hypoxia-Mediated Smooth Muscle Cell Proliferation Leading to Vascular Remodeling

Huang

Akgün

Mehmood

et al. 2022

BioMed Research International

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Vascular remodeling refers to changes in the size, contraction, distribution, and flow rate of blood vessels and even changes in vascular function. Vascular remodeling can cause cardiovascular and cerebrovascular diseases. It can also lead to other systemic diseases, such as pulmonary hypertension, pulmonary atherosclerosis, chronic obstructive pulmonary disease, stroke, and ascites of broilers. Hypoxia is one of the main causes of vascular remodeling. Prolonged hypoxia or intermittent hypoxia can lead to loss of lung ventilation, causing respiratory depression, irregular respiratory rhythms, and central respiratory failure. Animals that are unable to adapt to the highland environment are also prone to sustained constriction of the small pulmonary arteries, increased resistance to pulmonary circulation, and impaired blood circulation, leading to pulmonary hypertension and right heart failure if they live in a highland environment for long periods of time. However, limited studies have been found on the relationship between hypoxia and vascular remodeling. Therefore, this review will explore the relationship between hypoxia and vascular remodeling from the aspects of endoplasmic reticulum stress, mitochondrial dysfunction, abnormal calcium channel, disordered cellular metabolism, abnormal expression of miRNA, and other factors. This will help to understand the detailed mechanism of hypoxia-mediated smooth muscle cell proliferation and vascular remodeling for the better treatment and management of diseases due to vascular remodeling.

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“…The focus of this study was to identify sex-specific immune effectors that regulate obesity pathogenesis, focusing on the M2 macrophage signature gene Resistin-like molecule α (RELMα). RELMα is a small, secreted cysteine-rich protein that is expressed by macrophages primarily in response to Th2 cytokines, but can also be induced by hypoxia (34,35). RELMα has pleotropic functions ranging from inflammatory or immunoregulatory to microbicidal roles (36)(37)(38).…”

Section: Introductionmentioning

confidence: 99%

Sexual dimorphism in obesity is governed by RELMα regulation of adipose macrophages and eosinophils

Ruggiero-Ruff

et al. 2023

Preprint

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Obesity incidence is increasing worldwide with the urgent need to identify new therapeutics. Sex differences in immune cell activation drive obesity-mediated pathologies where males are more susceptible to obesity co-morbidities and exacerbated inflammation. Here, we demonstrate that the macrophage-secreted protein RELMα critically protects females against high fat diet-induced obesity. Compared to male mice, RELMα levels were elevated in both control and high fat dietfed females and correlated with adipose macrophages and eosinophils. RELMα-deficient females gained more weight and had pro-inflammatory macrophage accumulation and eosinophil loss, while both RELMα treatment and eosinophil transfer rescued this phenotype. Single cell RNAsequencing of the adipose stromal vascular fraction was performed and identified sex and RELMα-dependent changes. Genes involved in oxygen sensing and iron homeostasis, including hemoglobin and lncRNA Gm47283, correlated with increased obesity, while eosinophil chemotaxis and response to amyloid-beta were protective. Monocyte-to-macrophage transition was also dysregulated in RELMα-deficient animals. Collectively, these studies implicate a RELMα-macrophage-eosinophil axis in sex-specific protection against obesity and uncover new therapeutic targets for obesity.

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Hypoxia-Induced Mitogenic Factor: A Multifunctional Protein Involved in Health and Disease

Cited by 7 publications

References 55 publications

Identification of exercise‐regulated genes in mice exposed to cigarette smoke

Identification of exercise‐regulated genes in mice exposed to cigarette smoke

Mechanism of Hypoxia-Mediated Smooth Muscle Cell Proliferation Leading to Vascular Remodeling

Sexual dimorphism in obesity is governed by RELMα regulation of adipose macrophages and eosinophils

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