Galectin-3 mediates high-glucose-induced cardiomyocyte injury by the NADPH oxidase/reactive oxygen species pathway

Sun, Jingang; Zhang, Lijuan; Fang, Jian‑Hai; Yang, Shu; Chen, Lianghua

doi:10.1139/cjpp-2019-0708

Cited by 6 publications

(5 citation statements)

References 60 publications

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“…This protective effect was mediated by reduced oxidative stress and apoptosis. Pharmacologic Inhibition with MCP showed similar results ( Sun et al, 2020 ).…”

Section: Galectin-3 In Cardiovascular Diseasementioning

confidence: 55%

Unraveling the role of galectin-3 in cardiac pathology and physiology

Seropian,

Cassaglia,

Miksztowicz

et al. 2023

Front. Physiol.

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Galectin-3 (Gal-3) is a carbohydrate-binding protein with multiple functions. Gal-3 regulates cell growth, proliferation, and apoptosis by orchestrating cell-cell and cell-matrix interactions. It is implicated in the development and progression of cardiovascular disease, and its expression is increased in patients with heart failure. In atherosclerosis, Gal-3 promotes monocyte recruitment to the arterial wall boosting inflammation and atheroma. In acute myocardial infarction (AMI), the expression of Gal-3 increases in infarcted and remote zones from the beginning of AMI, and plays a critical role in macrophage infiltration, differentiation to M1 phenotype, inflammation and interstitial fibrosis through collagen synthesis. Genetic deficiency of Gal-3 delays wound healing, impairs cardiac remodeling and function after AMI. On the contrary, Gal-3 deficiency shows opposite results with improved remodeling and function in other cardiomyopathies and in hypertension. Pharmacologic inhibition with non-selective inhibitors is also protective in cardiac disease. Finally, we recently showed that Gal-3 participates in normal aging. However, genetic absence of Gal-3 in aged mice exacerbates pathological hypertrophy and increases fibrosis, as opposed to reduced fibrosis shown in cardiac disease. Despite some gaps in understanding its precise mechanisms of action, Gal-3 represents a potential therapeutic target for the treatment of cardiovascular diseases and the management of cardiac aging. In this review, we summarize the current knowledge regarding the role of Gal-3 in the pathophysiology of heart failure, atherosclerosis, hypertension, myocarditis, and ischemic heart disease. Furthermore, we describe the physiological role of Gal-3 in cardiac aging.

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“…This protective effect was mediated by reduced oxidative stress and apoptosis. Pharmacologic Inhibition with MCP showed similar results ( Sun et al, 2020 ).…”

Section: Galectin-3 In Cardiovascular Diseasementioning

confidence: 55%

Unraveling the role of galectin-3 in cardiac pathology and physiology

Seropian,

Cassaglia,

Miksztowicz

et al. 2023

Front. Physiol.

View full text Add to dashboard Cite

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“…The important role of Gal-3 in HF was first described by Sharma et al [5], which reported that this lectin was the strongest differentially regulated gene associated with HF. Subsequently, an increased level of myocardial Gal-3 has been observed in several animal models of heart disease [5,6,22,23] and in clinical settings [24][25][26][27]. Gal-3 is mainly expressed in activated macrophages and pathologically damaged cardiomyocytes and is considered as an active contributor to cardiac remodeling, including myocardial fibrogenesis, and to the development of HF [5].…”

Section: Discussionmentioning

confidence: 99%

Elevated plasma Galectin-3 is associated with major adverse kidney events and death after ICU admission

et al. 2022

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Background Galectin-3 (Gal-3) is a proinflammatory and profibrotic protein especially overexpressed after Acute Kidney Injury (AKI). The early renal prognostic value of Gal-3 after AKI in critically ill patients remains unexplored. The objective was to evaluate the prognostic value of plasma level of Gal-3 for Major Adverse Kidney Events (MAKE) and mortality 30 days after ICU admission across AKI stages. Methods This is an ancillary study of a prospective, observational, multicenter cohort (FROG-ICU). AKI was defined using KDIGO definition. Results Two thousand and seventy-six patients had a Gal-3 plasma level measurement at ICU admission. Seven hundred and twenty-three (34.8%) were females and the median age was 63 [51, 74] years. Eight hundred and seven (38.9%) patients developed MAKE, 774 (37.3%) had AKI and mortality rate at 30 days was 22.4% (N = 465). Patients who developed MAKE had higher Gal-3 level at admission compared to patients without (30.2 [20.8, 49.2] ng/ml versus 16.9 [12.7, 24.3] ng/ml, p < 0.001, respectively. The area under the receiver operating characteristic curve of Gal-3 to predict MAKE was 0.76 CI95% [0.74–0.78], p < 0.001. Gal-3 was associated with MAKE (OR 1.80 CI95% [1.68–1.93], p < 0.001, non-adjusted and OR 1.37 CI95% [1.27–1.49], p < 0.001, adjusted). The use of Gal-3 improved prediction performance of prediction model including SAPSII, Screatadm, pNGAL with a NRI of 0.27 CI95%(0.16–0.38), p < 0.001. Median Gal-3 was higher in non-survivors than in survivors at 30 days (29.2 [20.2, 49.2] ng/ml versus 18.8 [13.3, 29.2] ng/ml, p < 0.001, respectively). Conclusion Plasma levels of Gal-3 were strongly associated with renal function, with an increased risk of MAKE and death after ICU admission. Trial registration ClinicalTrials.gov NCT01367093. Registered on 6 June 2011. Graphical abstract

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“…He J et al reported that Gal-3 was involved in the production of ROS in cardiac fibroblasts by inducing NOX expression, especially NOX4 [ 44 ]. Similarly, Gal-3 stimulated the expression of NOX4 in cardiac myocytes and regulated the level of NOX4-derived ROS during myocardial fibrosis [ 45 ]. The interrelationship between Gal-3 and NOX4 in the oxidative stress of PF remains to be investigated.…”

Section: Discussionmentioning

confidence: 99%

Melatonin ameliorates bleomycin-induced pulmonary fibrosis via activating NRF2 and inhibiting galectin-3 expression

Lan

Cheng

et al. 2022

Acta Pharmacol Sin

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Pulmonary fibrosis (PF) is a chronic interstitial lung disease with no effective therapies. Galectin-3 (Gal-3), a marker of oxidative stress, plays a key role in the pathogenesis of PF. Fibroblast-myofibroblast differentiation (FMD) is an important source of fibrotic cells in PF. Previous studies showed that melatonin (MT) exerted anti-fibrotic effect in many diseases including PF through its antioxidant activity. In the present study we investigated the relationships among Gal-3, NRF2, ROS in FMD and their regulation by MT. We established an in vitro model of FMD in TGF-β1-treated human fetal lung fibroblast1 (HFL1) cells and a PF mouse model via bleomycin (BLM) intratracheal instillation. We found that Gal-3 expression was significantly increased both in vitro and in vivo. Knockdown of Gal-3 in HFL1 cells markedly attenuated TGF-β1-induced FMD process and ROS accumulation. In TGF-β1-treated HFL1 cells, pretreatment with NRF2-specific inhibitor ML385 (5 μM) significantly increased the levels of Gal-3, α-SMA and ROS, suggesting that the expression of Gal-3 was regulated by NRF2. Treatment with NRF2-activator MT (250 μM) blocked α-SMA and ROS accumulation accompanied by reduced Gal-3 expression. In BLM-induced PF model, administration of MT (5 mg·kg −1 ·d −1 , ip for 14 or 28 days) significantly attenuated the progression of lung fibrosis through up-regulating NRF2 and down-regulating Gal-3 expression in lung tissues. These results suggest that Gal-3 regulates TGF-β1-induced pro-fibrogenic responses and ROS production in FMD, and MT activates NRF2 to block FMD process by down-regulating Gal-3 expression. This study provides a useful clue for a clinical strategy to prevent PF. Graphic abstract of the mechanisms. MT attenuated BLM-induced PF via activating NRF2 and inhibiting Gal-3 expression.

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Galectin-3 mediates high-glucose-induced cardiomyocyte injury by the NADPH oxidase/reactive oxygen species pathway

Cited by 6 publications

References 60 publications

Unraveling the role of galectin-3 in cardiac pathology and physiology

Unraveling the role of galectin-3 in cardiac pathology and physiology

Elevated plasma Galectin-3 is associated with major adverse kidney events and death after ICU admission

Melatonin ameliorates bleomycin-induced pulmonary fibrosis via activating NRF2 and inhibiting galectin-3 expression

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