The Hedgehog Signaling Pathway in Idiopathic Pulmonary Fibrosis: Resurrection Time

The hedgehog (Hh) pathway is a sophisticated conserved cell signaling pathway that plays an essential role in controlling cell specification and proliferation, survival factors, and tissue patterning formation during embryonic development. Hh signal activity does not entirely disappear after development and may be reactivated in adulthood within tissue-injury-associated diseases, including idiopathic pulmonary fibrosis (IPF). The dysregulation of Hh-associated activating transcription factors, genomic abnormalities, and microenvironments is a co-factor that induces the initiation and progression of IPF.

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Involvement Of The Sonic Hedgehog Signaling Pathway In Idiopathic Pulmonary Fibrosis

10.1164/ajrccm-conference.2011.183.1_meetingabstracts.a3464 ◽

2011 ◽

Author(s):

Natacha Cigna ◽

Joëlle Marchal-Sommé ◽

Elika Farrokhi Moshai ◽

Lidwine Stervinou-Wémeau ◽

Monique Dehoux ◽

...

Keyword(s):

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Signaling Pathway ◽

Sonic Hedgehog ◽

Hedgehog Signaling ◽

Hedgehog Signaling Pathway ◽

Sonic Hedgehog Signaling ◽

Sonic Hedgehog Signaling Pathway

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Hedgehog-induced ciliary trafficking of kinesin-4 motor KIF7 requires intraflagellar transport but not KIF7’s microtubule binding

Molecular Biology of the Cell ◽

10.1091/mbc.e21-04-0215 ◽

2021 ◽

Author(s):

Yang Yue ◽

Martin F. Engelke ◽

T. Lynne Blasius ◽

Kristen J. Verhey

Keyword(s):

Transcription Factors ◽

Signaling Pathway ◽

Primary Cilium ◽

Hedgehog Signaling ◽

Intraflagellar Transport ◽

Hedgehog Signaling Pathway ◽

Microtubule Binding ◽

Pathway Activation ◽

Gli Transcription Factors ◽

Ciliary Localization

The kinesin-4 motor KIF7 is a conserved regulator of the Hedgehog signaling pathway. In vertebrates, Hedgehog signaling requires the primary cilium, and KIF7 and Gli transcription factors accumulate at the cilium tip in response to Hedgehog activation. Unlike conventional kinesins, KIF7 is an immotile kinesin and its mechanism of ciliary accumulation is unknown. We generated KIF7 variants with altered microtubule binding or motility. We demonstrate that microtubule binding of KIF7 is not required for the increase in KIF7 or Gli localization at the cilium tip in response to Hedgehog signaling. In addition, we show that the immotile behavior of KIF7 is required to prevent ciliary localization of Gli transcription factors in the absence of Hedgehog signaling. Using an engineered kinesin-2 motor that enables acute inhibition of intraflagellar transport (IFT), we demonstrate that kinesin-2 KIF3A/KIF3B/KAP mediates the translocation of KIF7 to the cilium tip in response to Hedgehog pathway activation. Together, these results suggest that KIF7’s role at the tip of the cilium is unrelated to its ability to bind to microtubules.

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Mechanism of Tripchlorolide Inhibiting Hedgehog Signaling Pathway to Delay Lung Fibrosis

Journal of Biomaterials and Tissue Engineering ◽

10.1166/jbt.2020.2346 ◽

2020 ◽

Vol 10 (7) ◽

pp. 992-998

Author(s):

Shirui Tan ◽

Qingrong Li ◽

Feifei Duan ◽

Qingqing Yuan ◽

Gang Deng

Keyword(s):

Signaling Pathway ◽

Lung Tissue ◽

Hedgehog Signaling ◽

Tissue Injury ◽

Collagen I ◽

Lung Fibroblasts ◽

Lung Injury Score ◽

Mouse Lung ◽

Hedgehog Signaling Pathway ◽

Gli 1

Background: The paper aimed to determine whether Tripchlorolide can exert anti-fibrotic effects by up-regulating Sufu to influence the Hedgehog signaling pathway, and to promote the application of Tripchlorolide in diseases associated with the Hedgehog signaling pathway. Material and Methods: In vivo experiment, bronchoalveolar lavage was performed on the 7th day after intratracheal instillation of bleomycin. The number of inflammatory cells and IL-6 levels were analyzed to observe the anti-inflammatory effect of Tripchlorolide. The lung tissues were obtained on the 14th day. The lung tissue injury was observed, and the expressions of a-SMA, collagen I, TGF-β i, Gli 1 and Sufu were determined. In vitro experiments, mouse lung was transfected with lentivirus to make fibroblasts. The Sufii was overexpressed, the changes in Gli 1 and Gli 2 levels were observed. The effects of the overexpressed Sufti of on the phenotype transformed a-SMA and collagen I levels in TGF-β 1 induced mouse lung fibroblasts were observed. Results: After administration with bleomycin, IL-6 level, total number of cells, neutrophils and macrophages in BALF of the Tripchlorolide group mice were reduced. The lung injury score, the expressions of lung tissue TGF-βl, a-SMA and Collagen I were low. The expression of Sufu was high, while the expression of Gli 1 was low. Compared with the groups in which cells were not transfected with lentivirus, the expression of Sufu in the transfected cells increased, and the expressions of Gli 1 and Gli 2 decreased. After stimulation with TGF-β Sufu decreased. Conclusion: Tripchlorolide can inhibit Hedgehog signaling pathway by up-regulating Sufu to exert an anti-fibrotic effect.

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The Roles of Hedgehog Signaling Pathway in Radioresistance of Cervical Cancer

Dose-Response ◽

10.1177/1559325819885293 ◽

2019 ◽

Vol 17 (4) ◽

pp. 155932581988529 ◽

Cited By ~ 4

Author(s):

Chang Liu ◽

Rensheng Wang

Keyword(s):

Cervical Cancer ◽

Drug Resistance ◽

Targeted Therapy ◽

Signaling Pathway ◽

Hedgehog Signaling ◽

Essential Role ◽

Hedgehog Signaling Pathway ◽

Advanced Cervical Cancer ◽

New Strategy ◽

The Relationship

Radiotherapy is an important treatment of cervical cancer, especially for advanced cervical cancer. According to research reports, Hedgehog signaling pathway plays an essential role in the growth, invasion, metastasis, recurrence, drug resistance, and radioresistance of cervical cancer. The components of Hedgehog signaling pathway could be biomarkers, related to progression and prognosis of cervical cancer. In addition, targeted therapy for Hedgehog signaling pathway is expected to become a new strategy for the treatment of radioresistant cervical cancer. This review summarizes the research status and progress of the relationship between radiation resistance and activation of Hedgehog signaling pathway in cervical cancer.

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