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A glycogen synthase kinase 3-like kinase MpGSK regulates cell differentiation in Marchantia polymorpha.

ABSTRACT: Plants precisely coordinate the balance between cell proliferation and differentiation to ensure the continuous development. In Arabidopsis thaliana, members of glycogen synthase kinase 3 (GSK3) family, which are highly conserved serine/threonine protein kinases among eukaryotes, play important roles in regulating cell proliferation and differentiation during various developmental processes. However, functional roles of GSK3s in the plant lineages except angiosperms remain to be elucidated. Here, we utilized a model liverwort, Marchantia polymorpha, for studies of GSK3, because it has a single GSK3-like kinase, MpGSK. When M. polymorpha was treated with a chemical compound, bikinin, which is known as a specific inhibitor for GSK3-like kinases, growth and morphologies were altered with an expansion of the meristematic region. Similarly, Mpgsk loss-of-function mutants accumulated undifferentiated cell mass with no differentiated tissues. By contrast, overexpression of MpGSK reduced the size of the meristem region. These results suggest that MpGSK plays important roles as a regulator for the balance between cell differentiation and proliferation in M. polymorpha.

SUBMITTER: Furuya T

PROVIDER: S-EPMC9200085 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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A glycogen synthase kinase 3-like kinase MpGSK regulates cell differentiation in <i>Marchantia polymorpha</i>.

Furuya Tomoyuki T Nishihama Ryuichi R Ishizaki Kimitsune K Kohchi Takayuki T Fukuda Hiroo H Kondo Yuki Y

Plant biotechnology (Tokyo, Japan) 20220301 1

Plants precisely coordinate the balance between cell proliferation and differentiation to ensure the continuous development. In <i>Arabidopsis thaliana</i>, members of glycogen synthase kinase 3 (GSK3) family, which are highly conserved serine/threonine protein kinases among eukaryotes, play important roles in regulating cell proliferation and differentiation during various developmental processes. However, functional roles of GSK3s in the plant lineages except angiosperms remain to be elucidate ...[more]

PMID: 35800965

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Project description:BackgroundChronic lung diseases such as asthma, COPD and pulmonary fibrosis are characterized by abnormal extracellular matrix (ECM) turnover. TGF-β is a key mediator stimulating ECM production by recruiting and activating lung fibroblasts and initiating their differentiation process into more active myofibroblasts. Glycogen synthase kinase-3 (GSK-3) regulates various intracellular signalling pathways; its role in TGF-β₁-induced myofibroblast differentiation is currently largely unknown.PurposeTo determine the contribution of GSK-3 signalling in TGF-β₁-induced myofibroblast differentiation.Experimental approachWe used MRC5 human lung fibroblasts and primary pulmonary fibroblasts of individuals with and without COPD. Protein and mRNA expression were determined by immunoblotting and RT-PCR analysis respectively.ResultsStimulation of MRC5 and primary human lung fibroblasts with TGF-β₁ resulted in time- and dose-dependent increases of α-sm-actin and fibronectin expression, indicative of myofibroblast differentiation. Pharmacological inhibition of GSK-3 by SB216763 dose-dependently attenuated TGF-β₁-induced expression of these myofibroblasts markers. Moreover, silencing of GSK-3 by siRNA or pharmacological inhibition by CT/CHIR99021 fully inhibited the TGF-β₁-induced expression of α-sm-actin and fibronectin. The effect of GSK-3 inhibition on α-sm-actin expression was similar in fibroblasts from individuals with and without COPD. Neither smad, NF-κB nor ERK1/2 were involved in the inhibitory actions of GSK-3 inhibition by SB126763 on myofibroblast differentiation. Rather, SB216763 increased the phosphorylation of CREB, which in its phosphorylated form acts as a functional antagonist of TGF-β/smad signalling.Conclusion and implicationWe demonstrate that GSK-3 signalling regulates TGF-β₁-induced myofibroblast differentiation by regulating CREB phosphorylation. GSK-3 may constitute a useful target for treatment of chronic lung diseases.

Dataset Information

A glycogen synthase kinase 3-like kinase MpGSK regulates cell differentiation in Marchantia polymorpha.

Publications

A glycogen synthase kinase 3-like kinase MpGSK regulates cell differentiation in <i>Marchantia polymorpha</i>.

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