Evaluation of prevention and treatment effects of fibroblast growth factor-21 in BLM-induced pulmonary fibrosis

Abstract

Pulmonary fibrosis is a progressive and fatal fibrotic lung disease and associated with a high mortality rate. In the study, the prevention and treatment effects of fibroblast growth factor-21 (FGF-21) in bleomycin (BLM)-induced pulmonary fibrosis were investigated in vivo and vitro. In the prevention of pulmonary fibrosis studies, the results showed that interdict of FGF-21 could reduce the related gene and protein expression levels of pulmonary fibrosis. In addition, FGF-21 significantly reduced both the aggregation of inflammatory cells and deposition of collagen in the lung by histopathology. In therapy of pulmonary fibrosis studies, the results indicated that treatment with FGF-21 resulted in an amelioration of the pulmonary fibrosis in mice with reductions of the pathological score, collagen deposition and transforming growth factor (TGF)-β and α-smooth muscle actin (α-SMA) expressions in the lung tissues at fibrotic stage, and late administration was also able to reduce the degree of pulmonary fibrosis and even better than these in the prevention group. Furthermore, BLM-induced THP-1 macrophage model was verified using FGF-21; the result showed that FGF-21 decreased the related gene expression level of pulmonary fibrosis. FGF-21 may have preventive and therapeutic effects on BLM-induced pulmonary fibrosis via inhibiting myofibroblast differentiation and inflammatory. Thus, FGF-21 represents a potential drug for the prevention and treatment of pulmonary fibrosis.

Crosstalk between fibroblasts and immunocytes in fibrosis: From molecular mechanisms to clinical trials

“…In pulmonary fibrosis, FGFs have been identified as therapeutic targets that trigger the activation and proliferation of fibroblasts but inhibit the differentiation of myofibroblasts 196,197 . Moreover, FGF‐21 can reduce the recruitment of immunocytes and ECM accumulation in pulmonary fibrosis 198 …”

AMPK signaling inhibits the differentiation of myofibroblasts: impact on age-related tissue fibrosis and degeneration

“…There is substantial evidence that the JAK/STAT3 pathway has a crucial role in many fibrotic diseases, e.g., systemic sclerosis, pulmonary fibrosis, and renal fibrosis (Pedroza et al 2016 ; Chakraborty et al 2017 ; Liu et al 2023 ). Currently, STAT3 inhibitors are promising drug candidates for different fibrotic diseases (Wang et al 2023a , b ; Xie et al 2023 ). JAK/STAT3 signaling has been associated with the activation of several cytokine receptors, such as those of IL-4, IL-6, IL-10, GM-CSF, as well as many growth factor receptors.…”

“…There are also certain endocrine factors, such as the klotho protein and fibroblast growth factor 21 (FGF21), which are recognized as anti-aging factors since they can attenuate many age-related degenerative processes, e.g., in the vascular system (Kurosu et al 2005 ; Mencke et al 2017a ; Salminen et al 2017a ). Interestingly, there are many studies indicating that the FGF21 and klotho proteins both possess anti-fibrotic properties in many fibrosis models (Mencke et al 2017b ; Ding et al 2019 ; Meng et al 2021 ; Wang et al 2023a , b ). For instance, Wang et al ( 2023a , b ) revealed that FGF21 exposure attenuated the extent of the bleomycin-induced pulmonary fibrosis in mice.…”

“…Interestingly, there are many studies indicating that the FGF21 and klotho proteins both possess anti-fibrotic properties in many fibrosis models (Mencke et al 2017b ; Ding et al 2019 ; Meng et al 2021 ; Wang et al 2023a , b ). For instance, Wang et al ( 2023a , b ) revealed that FGF21 exposure attenuated the extent of the bleomycin-induced pulmonary fibrosis in mice. Ding et al ( 2019 ) demonstrated that the soluble klotho protein reduced the severity of angiotensin II-induced cardiac fibrosis and hypetrophy in mice by inhibiting the TGF-β signaling pathway.…”

“…Ding et al ( 2019 ) demonstrated that the soluble klotho protein reduced the severity of angiotensin II-induced cardiac fibrosis and hypetrophy in mice by inhibiting the TGF-β signaling pathway. Currently, it is known that klotho and FGF21 proteins can affect several signaling pathways although it seems that the inhibition of TGF-β signaling might be involved in tissue fibrosis (Ding et al 2019 ; Wang et al 2023a , b ). There are several investigations indicating that both the klotho and FGF21 proteins are able to activate AMPK signaling in many experimental models (Salminen et al 2017b ; Luo et al 2023 ).…”