Inhibition of α-SMA by the Ectodomain of FGFR2c Attenuates Lung Fibrosis

Wang, Ju; Yu, Zhihong; Zhiyou, Zhou; Huang, Qin; Wang, Dingding; Sun, Li; Baowei, Zhu; Xing, Wei; He, Yi; An, Hongyu

doi:10.2119/molmed.2011.00425

Cited by 38 publications

(30 citation statements)

References 41 publications

(55 reference statements)

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“…Although this study showed a positive effect of Fgf2 on lung repair, it has also been reported that activation of FGFR signaling in pulmonary fibroblasts promotes fibrosis, as demonstrated by the reduced bleomycin-induced fibrosis in mice with combined inducible knockout of Fgfr1, Fgfr2 and Fgfr3 in fibroblasts (Guzy et al, 2017). A similar effect has been observed upon treatment of wild-type mice with a soluble Fgfr2c ligand trap, which inhibits signaling by the FGFs that activate stromal cells (Ju et al, 2012). Therefore, the repair-promoting effects of FGFs are unfortunately associated with induction of fibrosis through the action of FGFs on fibroblasts.…”

Section: Fgf Signaling In Lung Intestine and Liver Repair Fgf Signalsupporting

confidence: 68%

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Fibroblast growth factors: key players in regeneration and tissue repair

2017

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Tissue injury initiates a complex repair process, which in some organisms can lead to the complete regeneration of a tissue. In mammals, however, the repair of most organs is imperfect and results in scar formation. Both regeneration and repair are orchestrated by a highly coordinated interplay of different growth factors and cytokines. Among the key players are the fibroblast growth factors (FGFs), which control the migration, proliferation, differentiation and survival of different cell types. In addition, FGFs influence the expression of other factors involved in the regenerative response. Here, we summarize current knowledge on the roles of endogenous FGFs in regeneration and repair in different organisms and in different tissues and organs. Gaining a better understanding of these FGF activities is important for appropriate modulation of FGF signaling after injury to prevent impaired healing and to promote organ regeneration in humans.

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Section: Fgf Signaling In Lung Intestine and Liver Repair Fgf Signalsupporting

confidence: 68%

“…Reduces susceptibility to hyperoxia and promotes lung recovery Promotes alveolar regeneration in a long-term injury model Promotes recovery after bleomycin-induced or naphthalene-induced injury Hokuto et al, 2004Perl and Gale, 2009Guzy et al, 2015Guzy et al, 2017Ju et al, 2012 Continued…”

Section: Fgfr2b Fgf2mentioning

confidence: 99%

Fibroblast growth factors: key players in regeneration and tissue repair

2017

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“…Our results showed that the therapy of RAPA treatment for 14 d could ameliorate progressive pulmonary fibrosis, and the antifibrotic effects were more obvious in the lung tissues of the mice given RAPA for 28 d. The more rapid effect of RAPA compared with DHA (35 d) and naringin (21 d) suggests that RAPA treatment may have a more potent anti-fibrogenesis impact. The key effector cells in the development of pulmonary fibrosis are myofibroblasts (Wang et al, 2012), which are thought to arise from proliferation or differentiation of resident lung fibroblasts, epithelial-to-mesenchymal transition (EMT) and recruitment of circulating fibrocytes (Tulek et al, 2011;Kendall and Feghali-Bostwick, 2014). Various cytokines, growth factors, and signaling pathways are involved in these events.…”

Section: Discussionmentioning

confidence: 99%

“…TGF-β1 is a key fibrogenic cytokine, which plays a critical role in the expression of α-smooth muscle actin (α-SMA) and induction of lung fibrosis (Oka et al, 2013). α-SMA is the hallmark of myofibroblasts, which are generally considered to be the key effector cells in the development of fibrosis (Wang et al, 2012). The aim of this study was to evaluate RAPA treatment as a potential novel therapy for attenuating PQ-induced pulmonary fibrosis by assessing its effects on the survival rate, body weight, histology, and hydroxyproline (HYP) content of PQ-treated mice.…”

Section: Introductionmentioning

confidence: 99%

Effects of rapamycin against paraquat-induced pulmonary fibrosis in mice

Shao

Luo

et al. 2015

J. Zhejiang Univ. Sci. B

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Background and aims: Ingestion of paraquat (PQ), a widely used herbicide, can cause severe toxicity in humans, leading to a poor survival rate and prognosis. One of the main causes of death by PQ is PQ-induced pulmonary fibrosis, for which there are no effective therapies. The aim of this study was to evaluate the effects of rapamycin (RAPA) on inhibiting PQ-induced pulmonary fibrosis in mice and to explore its possible mechanisms. Methods: Male C57BL/6J mice were exposed to either saline (control group) or PQ (10 mg/kg body weight, intraperitoneally; test group). The test group was divided into four subgroups: a PQ group (PQ-exposed, non-treated), a PQ+RAPA group (PQ-exposed, treated with RAPA at 1 mg/kg intragastrically), a PQ+MP group (PQ-exposed, treated with methylprednisolone (MP) at 30 mg/kg intraperitoneally), and a PQ+MP+RAPA group (PQ-exposed, treated with MP at 30 mg/kg intraperitoneally and with RAPA at 1 mg/kg intragastrically). The survival rate and body weight of all the mice were recorded every day. Three mice in each group were sacrificed at 14 d and the rest at 28 d after intoxication. Lung tissues were excised and stained with hematoxylin-eosin (H&E) and Masson's trichrome stain for histopathological analysis. The hydroxyproline (HYP) content in lung tissues was detected using an enzyme-linked immunosorbent assay (ELISA) kit. The expression of transforming growth factor-β1 (TGF-β1) and α-smooth muscle actin (α-SMA) in lung tissues was detected by immunohistochemical staining and Western blotting. Results: A mice model of PQ-induced pulmonary fibrosis was established. Histological examination of lung tissues showed that RAPA treatment moderated the pathological changes of pulmonary fibrosis, including alveolar collapse and interstitial collagen deposition. HYP content in lung tissues increased soon after PQ intoxication but had decreased significantly by the 28th day after RAPA treatment. Immunohistochemical staining and Western blotting showed that RAPA treatment significantly down-regulated the enhanced levels of TGF-β1 and α-SMA in lung tissues caused by PQ exposure. However, RAPA treatment alone could not significantly ameliorate the lower survival rate and weight loss of treated mice. MP treatment enhanced the survival rate, but had no significant effects on attenuating PQ-induced pulmonary fibrosis or reducing the expression of TGF-β1 and α-SMA. Conclusions: This study demonstrates that RAPA treatment effectively suppresses PQ-induced alveolar collapse and collagen deposition in lung tissues through reducing the expression of TGF-β1 and α-SMA. Thus, RAPA has potential value in the treatment of PQ-induced pulmonary fibrosis.

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“…FGFR2c ligands are generally regarded as profibrotic, as they induce fibroblast proliferation and myofibroblast differentiation. Inhibition of FGFR2c ligand activity by overexpressing a decoy receptor inhibits smooth muscle actin ( Acta2 ) expression and attenuates bleomycin‐induced pulmonary fibrosis in mice (Ju et al, ; Yu et al, ). However, mesenchymal FGF signaling is not necessarily profibrotic.…”

Section: Introductionmentioning

confidence: 99%

Therapeutic and pathological roles of fibroblast growth factors in pulmonary diseases

Agha

Seeger

Bellusci

2016

Developmental Dynamics

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Fibroblast growth factors (FGFs) constitute a large family of polypeptides that are involved in many biological processes, ranging from prenatal cell-fate specification and organogenesis to hormonal and metabolic regulation in postnatal life. During embryonic development, these growth factors are important mediators of the crosstalk among ectoderm-, mesoderm-, and endoderm-derived cells, and they instruct the spatial and temporal growth of organs and tissues such as the brain, bone, lung, gut, and others. The involvement of FGFs in postnatal lung homeostasis is a growing field, and there is emerging literature about their roles in lung pathophysiology. In this review, the involvement of FGF signaling in a wide array of lung diseases will be summarized. Developmental Dynamics 246:235-244,

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Inhibition of α-SMA by the Ectodomain of FGFR2c Attenuates Lung Fibrosis

Cited by 38 publications

References 41 publications

Fibroblast growth factors: key players in regeneration and tissue repair

Fibroblast growth factors: key players in regeneration and tissue repair

Effects of rapamycin against paraquat-induced pulmonary fibrosis in mice

Therapeutic and pathological roles of fibroblast growth factors in pulmonary diseases

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