The Hedgehog Signaling Pathway in Idiopathic Pulmonary Fibrosis: Resurrection Time

Effendi, Wiwin Is; Nagano, Tatsuya

doi:10.3390/ijms23010171

Cited by 27 publications

(16 citation statements)

References 151 publications

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“…In the canonical pathway, the binding of Hh to ptch1 relieves the inhibitory effect of ptch1 on Smo. Then, Smo is transferred to the plasma membrane and participates in the regulation of genes in the nucleus by activating full-length Gli to become Gli1/2/3 (active form), thereby inducing AEC apoptosis, fibroblast differentiation, EMT, and M2 polarization (Effendi and Nagano, 2021). In the non-canonical pathway (Type I), the binding of Hh to ptch1 prevents cyclin B1 from recruiting proapoptotic complexes, thereby failing to activate caspasemediated apoptosis.…”

Section: Developmental Pathways: Hedgehog Wnt and Notchmentioning

confidence: 99%

“…In the non-canonical pathway (Type I), the binding of Hh to ptch1 prevents cyclin B1 from recruiting proapoptotic complexes, thereby failing to activate caspasemediated apoptosis. After entering the nucleus, cyclin B1 can also regulate cell cycle progression by promoting cell proliferation (Robbins et al, 2012;Effendi and Nagano, 2021). In the noncanonical pathway (Type II), the coupling of Smo to Gi protein activates downstream PI3K, Rho, and Rac1, leading to an increase in intracellular calcium concentration and cytoskeleton rearrangement (Robbins et al, 2012;Effendi and Nagano, 2021).…”

Section: Developmental Pathways: Hedgehog Wnt and Notchmentioning

confidence: 99%

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Targeting Growth Factor and Cytokine Pathways to Treat Idiopathic Pulmonary Fibrosis

Liu

et al. 2022

Front. Pharmacol.

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Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial lung disease of unknown origin that usually results in death from secondary respiratory failure within 2–5 years of diagnosis. Recent studies have identified key roles of cytokine and growth factor pathways in the pathogenesis of IPF. Although there have been numerous clinical trials of drugs investigating their efficacy in the treatment of IPF, only Pirfenidone and Nintedanib have been approved by the FDA. However, they have some major limitations, such as insufficient efficacy, undesired side effects and poor pharmacokinetic properties. To give more insights into the discovery of potential targets for the treatment of IPF, this review provides an overview of cytokines, growth factors and their signaling pathways in IPF, which have important implications for fully exploiting the therapeutic potential of targeting cytokine and growth factor pathways. Advances in the field of cytokine and growth factor pathways will help slow disease progression, prolong life, and improve the quality of life for IPF patients in the future.

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Section: Developmental Pathways: Hedgehog Wnt and Notchmentioning

confidence: 99%

Section: Developmental Pathways: Hedgehog Wnt and Notchmentioning

confidence: 99%

Targeting Growth Factor and Cytokine Pathways to Treat Idiopathic Pulmonary Fibrosis

Liu

et al. 2022

Front. Pharmacol.

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“…Multiple cellular signaling pathways play a crucial role in the development of IPF. JAK/STAT signaling ( Montero et al, 2021 ), receptor-type tyrosine kinase/non-receptor-type tyrosine kinase signaling (e.g., Src) ( Hu et al, 2014 ), PI3K/Akt/mTOR signaling ( Hennessy et al, 2005 ; Mercer et al, 2016 ; Lawrence and Nho, 2018 ), and Hedgehog signaling ( Effendi and Nagano, 2021 ) comprise complex fibrosis regulatory signaling pathway. In our previous reviews, we have discussed the aforementioned signaling pathways ( Ma et al, 2022 ).…”

Section: Recent Progress In Therapeutic Targets and New Drug Developm...mentioning

confidence: 99%

Research Progress in the Molecular Mechanisms, Therapeutic Targets, and Drug Development of Idiopathic Pulmonary Fibrosis

et al. 2022

Front. Pharmacol.

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Idiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung disease. Recent studies have identified the key role of crosstalk between dysregulated epithelial cells, mesenchymal, immune, and endothelial cells in IPF. In addition, genetic mutations and environmental factors (e.g., smoking) have also been associated with the development of IPF. With the recent development of sequencing technology, epigenetics, as an intermediate link between gene expression and environmental impacts, has also been reported to be implicated in pulmonary fibrosis. Although the etiology of IPF is unknown, many novel therapeutic targets and agents have emerged from clinical trials for IPF treatment in the past years, and the successful launch of pirfenidone and nintedanib has demonstrated the promising future of anti-IPF therapy. Therefore, we aimed to gain an in-depth understanding of the underlying molecular mechanisms and pathogenic factors of IPF, which would be helpful for the diagnosis of IPF, the development of anti-fibrotic drugs, and improving the prognosis of patients with IPF. In this study, we summarized the pathogenic mechanism, therapeutic targets and clinical trials from the perspective of multiple cell types, gene mutations, epigenetic and environmental factors.

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“…TGF-β can also induce the transcription of GLI2 (an activator of Hedgehog signaling), which subsequently upregulates Hedgehog-targeted profibrotic gene ( e.g. , α-SMA) expression ( 26 – 28 ). In contrast, BMP-7 activates Smad1/5/8, which can block the nuclear translocation of phosphorylated receptor-Smad2/3 and thus inhibit TGF-β signaling ( 29 ).…”

Section: Pathology and Current Therapies Of Fibrosismentioning

confidence: 99%

Extracellular vesicles as advanced therapeutics for the resolution of organ fibrosis: Current progress and future perspectives

Wang

Lou

et al. 2022

Front. Immunol.

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Organ fibrosis is a serious health challenge worldwide, and its global incidence and medical burden are increasing dramatically each year. Fibrosis can occur in nearly all major organs and ultimately lead to organ dysfunction. However, current clinical treatments cannot slow or reverse the progression of fibrosis to end-stage organ failure, and thus advanced anti-fibrotic therapeutics are urgently needed. As a type of naturally derived nanovesicle, native extracellular vesicles (EVs) from multiple cell types (e.g., stem cells, immune cells, and tissue cells) have been shown to alleviate organ fibrosis in many preclinical models through multiple effective mechanisms, such as anti-inflammation, pro-angiogenesis, inactivation of myofibroblasts, and fibrinolysis of ECM components. Moreover, the therapeutic potency of native EVs can be further enhanced by multiple engineering strategies, such as genetic modifications, preconditionings, therapeutic reagent-loadings, and combination with functional biomaterials. In this review, we briefly introduce the pathology and current clinical treatments of organ fibrosis, discuss EV biology and production strategies, and particularly focus on important studies using native or engineered EVs as interventions to attenuate tissue fibrosis. This review provides insights into the development and translation of EV-based nanotherapies into clinical applications in the future.

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The Hedgehog Signaling Pathway in Idiopathic Pulmonary Fibrosis: Resurrection Time

Cited by 27 publications

References 151 publications

Targeting Growth Factor and Cytokine Pathways to Treat Idiopathic Pulmonary Fibrosis

Targeting Growth Factor and Cytokine Pathways to Treat Idiopathic Pulmonary Fibrosis

Research Progress in the Molecular Mechanisms, Therapeutic Targets, and Drug Development of Idiopathic Pulmonary Fibrosis

Extracellular vesicles as advanced therapeutics for the resolution of organ fibrosis: Current progress and future perspectives

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