Endogenous tryptophan metabolite 5-Methoxytryptophan inhibits pulmonary fibrosis by downregulating the TGF-β/SMAD3 and PI3K/AKT signaling pathway

Fang, Le; Chen, Hongtao; Kong, Renyi; Que, Jun

doi:10.1016/j.lfs.2020.118399

Cited by 27 publications

(23 citation statements)

References 37 publications

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“…A great number of studies indicated that phosphatidylinositol-3-kinase (PI3K) was involved in the pathomechanism of pulmonary fibrosis (51)(52)(53)(54).…”

Section: Pi3k-relevant Signaling Pathwaymentioning

confidence: 99%

TGF‑β1: Gentlemanly orchestrator in idiopathic pulmonary fibrosis (Review)

2021

Int J Mol Med

122

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Idiopathic pulmonary fibrosis (IPF) is a worldwide disease characterized by the chronic and irreversible decline of lung function. Currently, there is no drug to successfully treat the disease except for lung transplantation. Numerous studies have been devoted to the study of the fibrotic process of IPF and findings showed that transforming growth factor-β1 (TGF-β1) plays a central role in the development of IPF. TGF-β1 promotes the fibrotic process of IPF through various signaling pathways, including the Smad, MAPK, and ERK signaling pathways. There are intersections between these signaling pathways, which provide new targets for researchers to study new drugs. In addition, TGF-β1 can affect the fibrosis process of IPF by affecting oxidative stress, epigenetics and other aspects. Most of the processes involved in TGF-β1 promote IPF, but TGF-β1 can also inhibit it. This review discusses the role of TGF-β1 in IPF. Contents1. Introduction 2. TGF-β1-involved pathway in IPF 3. Discussion 4. Conclusion

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“…A great number of studies indicated that phosphatidylinositol-3-kinase (PI3K) was involved in the pathomechanism of pulmonary fibrosis (51)(52)(53)(54).…”

Section: Pi3k-relevant Signaling Pathwaymentioning

confidence: 99%

TGF‑β1: Gentlemanly orchestrator in idiopathic pulmonary fibrosis (Review)

2021

Int J Mol Med

122

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“…It disrupted TGFβ/SMAD3 and PI-3K/Akt pathways. In vitro experiments provide evidence to support the observation that 5-MTP inhibits fibroblast differentiation to myofibroblasts and reduces fibroblast migration by blocking TGFβ signaling pathway ( Fang et al, 2020 ). These findings suggest that 5-MTP is effective in attenuating pulmonary fibrosis due to external injury.…”

Section: -Mtp Inhibits Bleomycin-induced Pulmonary Fibrosismentioning

confidence: 63%

“…Taken together, the reported data suggest that 5-MTP exerts its multiple protective effects through blocking p38 MAPK activation and p38 MAPK signaling pathways. Fang et al reported that 5-MTP attenuates pulmonary fibrosis by blocking TGFβ-induced SMAD3 and PI3K/AKT signaling pathways (Fang et al, 2020). Thus, 5-MTP controls tissue fibrosis by inhibiting several pro-fibrotic signaling pathways (Figure 4).…”

Section: -Mtp Disrupts Pro-fibrotic Signaling Pathwaysmentioning

confidence: 98%

“…Recent advances in the cellular and molecular mechanisms of lung fibrosis provide evidence to indicate that pulmonary fibrosis shares with fibrosis of other organs key pathological features such as recruitment of monocytes to promote fibrosis, conversion of resident fibroblasts to myofibroblasts and activation of pro-fibrotic transcriptional programs ( Zepp et al, 2017 ; Peyser et al, 2019 ). It is thus not unexpected that 5-MTP inhibits bleomycin-induced pulmonary fibrosis in a murine model ( Fang et al, 2020 ). In this model, Fang et al showed that 5-MTP administration to bleomycin-treated mice reduced collagen deposition, myofibroblasts accumulation and alveolar architectural destruction.…”

Section: -Mtp Inhibits Bleomycin-induced Pulmonary Fibrosismentioning

confidence: 99%

“…A number of signaling pathways including p38 MAPK ( Ma et al, 1999 ; Stambe et al, 2004 ; Molkentin et al, 2017 ; Turner and Blythe, 2019 ), TGFβ/SMAD3 ( Fang et al, 2020 ), PI3K/AKT ( Zhang et al, 2016 ; Hsu et al, 2017 ; Fang et al, 2020 ; Hu et al, 2020 ); JNK ( Grynberg et al, 2017 ) and STAT3 ( Chakraborty et al, 2017 ) were reported to mediate tissue fibrosis. p38 MAPK plays a central regulatory role.…”

Section: Potential Mechanisms By Which 5-mtp Controls Fibrosismentioning

confidence: 99%

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Control of Tissue Fibrosis by 5-Methoxytryptophan, an Innate Anti-Inflammatory Metabolite

2021

Front. Pharmacol.

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Tissue fibrosis causes debilitating human diseases such as liver cirrhosis, heart failure, chronic kidney disease and pulmonary insufficiency. It is a dynamic process orchestrated by specific subsets of monocyte-macrophages, fibroblasts, pericytes and hepatic stellate cells. Fibrosis is linked to tissue inflammation. Pro-inflammatory macrophages promote fibrosis by driving myofibroblast differentiation and macrophage myofibroblast transition. Myofibroblasts express α-smooth muscle cell actin (α-SMA) and secrete extracellular matrix (ECM) proteins notably collagen I and III. Deposition of ECM proteins at injury sites and interstitial tissues distorts normal structure and impairs vital functions. Despite advances in the mechanisms of fibrosis at cellular, molecular and genetic levels, prevention and treatment of fibrotic diseases remain poorly developed. Recent reports suggest that 5-methoxytryptophan (5-MTP) is effective in attenuating injury-induced liver, kidney, cardiac and pulmonary fibrosis. It inhibits macrophage activation and blocks fibroblast differentiation to myofibroblasts. Furthermore, it inhibits hepatic stellate cell differentiation into myofibroblasts. As 5-MTP is an endogenous molecule derived from tryptophan catabolism via tryptophan hydroxylase pathway, it is well-suited as a lead compound for developing new anti-fibrotic drugs. This article provides an overview of 5-MTP synthesis, and a critical review of its anti-fibrotic activities. Its mechanisms of actions and potential therapeutic value will be discussed.

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5-Methoxytryptophan ameliorates endotoxin-induced acute lung injury in vivo and in vitro by inhibiting NLRP3 inflammasome-mediated pyroptosis through the Nrf2/HO-1 signaling pathway

Wang

et al. 2023

Inflamm. Res.

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Endogenous tryptophan metabolite 5-Methoxytryptophan inhibits pulmonary fibrosis by downregulating the TGF-β/SMAD3 and PI3K/AKT signaling pathway

Cited by 27 publications

References 37 publications

TGF‑β1: Gentlemanly orchestrator in idiopathic pulmonary fibrosis (Review)

TGF‑β1: Gentlemanly orchestrator in idiopathic pulmonary fibrosis (Review)

Control of Tissue Fibrosis by 5-Methoxytryptophan, an Innate Anti-Inflammatory Metabolite

5-Methoxytryptophan ameliorates endotoxin-induced acute lung injury in vivo and in vitro by inhibiting NLRP3 inflammasome-mediated pyroptosis through the Nrf2/HO-1 signaling pathway

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