FGF21 attenuates pulmonary fibrogenesis through ameliorating oxidative stress in vivo and in vitro

Zhang, Shengqi; Yu, Dan; Wang, Mengxia; Huang, Tao; Wu, Huijun; Zhang, Yu; Zhang, Teng; Wang, Wenfei; Yin, Jun; Ren, Guangxin; Li, Deshan

doi:10.1016/j.biopha.2018.03.100

Cited by 41 publications

(32 citation statements)

References 43 publications

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“…Our previous study found that the generation of Hyp, Col‐I, and Col‐III are involved in pulmonary fibrosis induced by Nano NiO in rats . Col‐I increased significantly when A549 cells were treated with paraquat . In the present study, Nano NiO markedly elevated the contents of Col‐I and Hyp, implying that the collagen excessive formation model in A549 cells was successfully established.…”

Section: Discussionsupporting

confidence: 69%

“…5 Col-I increased significantly when A549 cells were treated with paraquat. 36 In the present study, Nano NiO markedly elevated the contents of Col-I and Hyp, implying that the collagen excessive formation model in A549 cells was successfully established. It has been demonstrated that TGF-β1, as a member of TGF-β superfamily, secreted cytokines that were involved in cellular processes via ligand-receptor binding.…”

Section: Discussionsupporting

confidence: 59%

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TGF‐β1 mediated MAPK signaling pathway promotes collagen formation induced by Nano NiO in A549 cells

Tian

Chang

Zhang

et al. 2019

Environmental Toxicology

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Nickel oxide nanoparticles (Nano NiO) could induce pulmonary fibrosis, however, the mechanisms are still unknown. The aim of the present study was to explore the roles of transforming growth factor‐β1 (TGF‐β1), mitogen‐activated protein kinase (MAPK) pathway and MMPs/TIMPs balance in Nano NiO‐induced pulmonary fibrosis. For that purpose, we first established Nano NiO‐induced human lung adenocarcinoma epithelial cells (A549 cells) model of collagen excessive formation through detecting the levels of hydroxyproline (Hyp) and type I collagen (Col‐I). Then the protein levels of TGF‐β1, MAPKs, and MMPs/TIMPs were assessed by Western blot. The results showed that Nano NiO resulted in the increased contents of Hyp, Col‐I, and TGF‐β1, the MAPK pathway activation and MMPs/TIMPs imbalance with a dose‐dependent manner. In addition, to investigate whether TGF‐β1 mediated MAPK signaling pathway, A549 cells were treated by 100 μg/mL Nano NiO combined with TGF‐β1, p38 MAPK, and ERK1/2 inhibitors (10 μM SB431542, 10 μM SB203580, and 10 μM U0126), respectively. We found that MAPK signal pathway was suppressed by TGF‐β1 inhibitor. Meanwhile, the increased contents of Hyp and Col‐I, and MMPs/TIMPs imbalance were alleviated by the p38 MAPK and ERK1/2 inhibitors, respectively. These findings indicated that the MAPK pathway and MMPs/TIMPs imbalance were involved in collagen excessive formation induced by Nano NiO.

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Section: Discussionsupporting

confidence: 69%

Section: Discussionsupporting

confidence: 59%

TGF‐β1 mediated MAPK signaling pathway promotes collagen formation induced by Nano NiO in A549 cells

Tian

Chang

Zhang

et al. 2019

Environmental Toxicology

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“…Administration or overexpression of FGF21 reduces murine renal fibrosis in a diabetic model ( 222 ) and a ureteral obstruction model ( 223 ). Likewise, FGF21 administration inhibits formation of bleomycin-induced pulmonary fibrosis in vivo by suppressing oxidative stress via NRF2 activation, and inhibiting TGF-β-induced activation of pulmonary myofibroblasts ( 224 ).…”

Section: Potential Of Fibroblast Growth Factor 21 Physiology As a Thementioning

confidence: 99%

FGF21: An Emerging Therapeutic Target for Non-Alcoholic Steatohepatitis and Related Metabolic Diseases

2020

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The rising global prevalence of obesity, metabolic syndrome, and type 2 diabetes has driven a sharp increase in non-alcoholic fatty liver disease (NAFLD), characterized by excessive fat accumulation in the liver. Approximately one-sixth of the NAFLD population progresses to non-alcoholic steatohepatitis (NASH) with liver inflammation, hepatocyte injury and cell death, liver fibrosis and cirrhosis. NASH is one of the leading causes of liver transplant, and an increasingly common cause of hepatocellular carcinoma (HCC), underscoring the need for intervention. The complex pathophysiology of NASH, and a predicted prevalence of 3–5% of the adult population worldwide, has prompted drug development programs aimed at multiple targets across all stages of the disease. Currently, there are no approved therapeutics. Liver-related morbidity and mortality are highest in more advanced fibrotic NASH, which has led to an early focus on anti-fibrotic approaches to prevent progression to cirrhosis and HCC. Due to limited clinical efficacy, anti-fibrotic approaches have been superseded by mechanisms that target the underlying driver of NASH pathogenesis, namely steatosis, which drives hepatocyte injury and downstream inflammation and fibrosis. Among this wave of therapeutic mechanisms targeting the underlying pathogenesis of NASH, the hormone fibroblast growth factor 21 (FGF21) holds considerable promise; it decreases liver fat and hepatocyte injury while suppressing inflammation and fibrosis across multiple preclinical studies. In this review, we summarize preclinical and clinical data from studies with FGF21 and FGF21 analogs, in the context of the pathophysiology of NASH and underlying metabolic diseases.

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“…Replenishment of FGF21 protects against atherosclerosis indirectly by inducing adipose tissue production of adiponectin and suppressing the hepatic cholesterol synthesis, leading to attenuation of hypercholesterolemia [94], and directly by preventing ER stress-mediated apoptosis of endothelial cells and macrophages [95], enhancing cholesterol efflux from macrophages blocking its conversion to foam cells [96, 97], and inhibiting smooth muscle cells proliferation and calcification [98, 99]. Finally, limited data suggest protective actions of FGF21 in the lung, attenuating fibrosis though activating the Nrf2 pathway, and in a sepsis model by enhancing animal survival [100–102]. …”

Section: Fgf21 In Preclinical Experimental Animal Studiesmentioning

confidence: 99%

Fibroblast growth factor 21 in chronic kidney disease

et al. 2018

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Fibroblast growth factor 21 (FGF21) is a member of the endocrine FGF family that acts as a metabolic regulator of both glucose and lipid metabolism. Similar to fibroblast growth factor 23 (FGF23), serum FGF21 levels rise progressively with the loss of renal function, reaching 20 times normal values in end-stage renal disease. In patients with chronic kidney disease (CKD), higher serum FGF21 levels correlate with poorer metabolic profile, higher inflammatory markers, more comorbidities, and higher mortality. The high serum FGF21 levels are above and beyond what can be explained by the loss of FGF21 renal clearance, suggesting increased production and/or impaired non-renal clearance. In diabetic nephropathy, serum FGF21 levels correlate with the severity of albuminuria and faster loss of glomerular filtrate rate and can potentially be a biomarker of poor prognostic. The observational and associative human data contrast sharply with in vitro and in vivo preclinical experimental data, which is more in line with a protective role of FGF21 in chronic nephropathies. We here review the physiology of FGF21, and the literature regarding its behavior in CKD with particular focus on diabetic nephropathy. Finally, we speculate on the role of FGF21 in CKD.

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FGF21 attenuates pulmonary fibrogenesis through ameliorating oxidative stress in vivo and in vitro

Cited by 41 publications

References 43 publications

TGF‐β1 mediated MAPK signaling pathway promotes collagen formation induced by Nano NiO in A549 cells

TGF‐β1 mediated MAPK signaling pathway promotes collagen formation induced by Nano NiO in A549 cells

FGF21: An Emerging Therapeutic Target for Non-Alcoholic Steatohepatitis and Related Metabolic Diseases

Fibroblast growth factor 21 in chronic kidney disease

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