Decision letter for "BMP-Smad Signaling Regulates Postnatal Crown Dentinogenesis in Mouse Molar"

2019 ◽  
Keyword(s):  
Smad Signaling

Author response for "BMP-Smad Signaling Regulates Postnatal Crown Dentinogenesis in Mouse Molar"

2019 ◽  
Author(s):  
Maiko Omi ◽  
Anshul K. Kulkarni ◽  
Anagha Raichur ◽  
Mason Fox ◽  
Amber Uptergrove ◽  
...  
Keyword(s):  
Author Response ◽  
Smad Signaling

scholarly journals USP9X-mediated KDM4C deubiquitination promotes lung cancer radioresistance by epigenetically inducing TGF-β2 transcription

2021 ◽  
Author(s):  
Xiaohua Jie ◽  
William Pat Fong ◽  
Rui Zhou ◽  
Ye Zhao ◽  
Yingchao Zhao ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Affinity Purification ◽  
Smad Signaling ◽  
Lung Cancer Patients ◽  
Lysine Specific Demethylase ◽  
Underlying Mechanisms ◽  
H3k9me3 Level ◽  
Critical Binding

AbstractRadioresistance is regarded as the main barrier to effective radiotherapy in lung cancer. However, the underlying mechanisms of radioresistance remain elusive. Here, we show that lysine-specific demethylase 4C (KDM4C) is overexpressed and correlated with poor prognosis in lung cancer patients. We provide evidence that genetical or pharmacological inhibition of KDM4C impairs tumorigenesis and radioresistance in lung cancer in vitro and in vivo. Moreover, we uncover that KDM4C upregulates TGF-β2 expression by directly reducing H3K9me3 level at the TGF-β2 promoter and then activates Smad/ATM/Chk2 signaling to confer radioresistance in lung cancer. Using tandem affinity purification technology, we further identify deubiquitinase USP9X as a critical binding partner that deubiquitinates and stabilizes KDM4C. More importantly, depletion of USP9X impairs TGF-β2/Smad signaling and radioresistance by destabilizing KDM4C in lung cancer cells. Thus, our findings demonstrate that USP9X-mediated KDM4C deubiquitination activates TGF-β2/Smad signaling to promote radioresistance, suggesting that targeting KDM4C may be a promising radiosensitization strategy in the treatment of lung cancer.

scholarly journals Concurrent YAP/TAZ and SMAD signaling mediate vocal fold fibrosis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ryosuke Nakamura ◽  
Nao Hiwatashi ◽  
Renjie Bing ◽  
Carina P. Doyle ◽  
Ryan C. Branski
Keyword(s):  
Vocal Fold ◽  
Vocal Folds ◽  
Nuclear Accumulation ◽  
Smad Pathway ◽  
Surgical Interventions ◽  
Smad Signaling ◽  
Iatrogenic Damage ◽  
Tgf Β1

AbstractVocal fold (VF) fibrosis is a major cause of intractable voice-related disability and reduced quality of life. Excision of fibrotic regions is suboptimal and associated with scar recurrence and/or further iatrogenic damage. Non-surgical interventions are limited, putatively related to limited insight regarding biochemical events underlying fibrosis, and downstream, the lack of therapeutic targets. YAP/TAZ integrates diverse cell signaling events and interacts with signaling pathways related to fibrosis, including the TGF-β/SMAD pathway. We investigated the expression of YAP/TAZ following vocal fold injury in vivo as well as the effects of TGF-β1 on YAP/TAZ activity in human vocal fold fibroblasts, fibroblast-myofibroblast transition, and TGF-β/SMAD signaling. Iatrogenic injury increased nuclear localization of YAP and TAZ in fibrotic rat vocal folds. In vitro, TGF-β1 activated YAP and TAZ in human VF fibroblasts, and inhibition of YAP/TAZ reversed TGF-β1-stimulated fibroplastic gene upregulation. Additionally, TGF-β1 induced localization of YAP and TAZ in close proximity to SMAD2/3, and nuclear accumulation of SMAD2/3 was inhibited by a YAP/TAZ inhibitor. Collectively, YAP and TAZ were synergistically activated with the TGF-β/SMAD pathway, and likely essential for the fibroplastic phenotypic shift in VF fibroblasts. Based on these data, YAP/TAZ may evolve as an attractive therapeutic target for VF fibrosis.

Tectona grandis Leaf Extract Ameliorates Hepatic Fibrosis: Modulation of TGF- β /Smad Signaling Pathway and Upregulating MMP3/TIMP1 Ratio

2021 ◽  
pp. 113938
Author(s):  
Somayya Tariq ◽  
Koloko Brice Landry ◽  
Ayesha Malik ◽  
Sidra Rehman ◽  
Bushra Ijaz ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Hepatic Fibrosis ◽  
Leaf Extract ◽  
Tectona Grandis ◽  
Smad Signaling ◽  
Smad Signaling Pathway
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