The essential role of TAZ in normal tissue homeostasis

Jeong, Mi Gyeong; Kim, Hyo Kyeong; Hwang, Eun Sook

doi:10.1007/s12272-021-01322-w

Cited by 13 publications

(13 citation statements)

References 88 publications

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“…Our results confirmed that TAZ promoted microglial migration in vitro. Moreover, treatment with XMU-MP-1 (an inhibitor of Hippo kinase MST1/2 to activate TAZ) facilitated the migration and accumulation of microglia to form microglial scars at the lesion border and improved the functional recovery of mice after SCI, which was consistent with other studies reporting that TAZ can promote the migration of cells (Jeong, Kim et al, 2021). However, the specific effect of TAZ on functional recovery and the formation of microglial scars following SCI should be further confirmed utilizing microglial TAZ-conditional knockout (CKO) transgenic mice.…”

Section: Discussionsupporting

confidence: 90%

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TAZ Induces Migration of Microglia and Promotes Neurological Recovery After Spinal Cord Injury

Huang

et al. 2022

Front. Pharmacol.

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Following spinal cord injury (SCI), microglia gradually migrate to the edge of the lesion, interweaving around the border of the lesion to form the microglial scar, which performs inflammatory limiting and neuroprotective functions. Recent reports showed that Yes-associated protein (YAP) was expressed in astrocytes and promoted the formation of astrocytic scars, while YAP was not expressed in microglia after SCI. YAP and its paralogue transcriptional coactivator with PDZ-binding motif (TAZ) are transcriptional coactivators, which have a similar functional role as both are negatively regulated by the Hippo signalling pathway. However, the expression and function of TAZ after SCI are unclear. Our research group previously found that Fascin-1 was highly expressed in microglia and promoted migration of microglia after SCI, and that, there was a close regulatory relationship between Fascin-1 and YAP/TAZ. In this study, we demonstrated that TAZ was significantly upregulated and mainly expressed in microglia after SCI, and accumulated in the nuclei of microglia in the spinal cord at 14 days post-SCI. Moreover, TAZ was upregulated and accumulated in the nuclei of anti-inflammatory M2-like (M2-L) polarized or myelin-treated microglia. Additionally, XMU-MP-1 (an inhibitor of the Hippo kinase MST1/2 to active TAZ) promoted the aggregation of microglia around the lesion core, resulting in the formation of microglial scars and the functional recovery of mice after SCI. Our findings also indicated that TAZ promoted microglial migration in vitro. Mechanistically, Fascin-1 interacted with TAZ, which upregulated TAZ expression and induced TAZ nuclear accumulation in microglia to promote microglial migration. These findings revealed that TAZ mediated microglial migration to the edge of the lesion core, promoting the formation of microglial scars and functional recovery after SCI. Moreover, TAZ was downstream of Fascin-1, which positively regulated microglial migration after SCI.

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Section: Discussionsupporting

confidence: 90%

“…Furthermore, suppression of LATS1 facilitated astrocyte proliferation after SCI ( Wang and Chen 2018 ). YAP/TAZ are the core components of the Hippo pathway and regulate related target genes for tumour invasion and metastasis ( Jeong, Kim et al, 2021 ). YAP mainly promoted astrocytic proliferation after SCI ( Xie, Shen et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

TAZ Induces Migration of Microglia and Promotes Neurological Recovery After Spinal Cord Injury

Huang

et al. 2022

Front. Pharmacol.

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“…For instance, the possibility that Taz may compensate for Yap in the intestinal crypts of Yap knockout mice has been raised ( Barry et al, 2013 ). On the other hand, despite their similarities, there is growing evidence that they can be distinguished by structural and functional aspects ( Jeong et al, 2021 ; Reggiani et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Src family kinases inhibit differentiation of intestinal epithelial cells through the Hippo effector YAP1

Fallah

Beaulieu

2021

Biology Open

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Intestinal cell lineage differentiation is a tightly regulated mechanism that involves several intracellular signaling pathways affecting the expression of a variety of transcription factors, which ultimately regulate cell specific gene expression. Absorptive and goblet cells are the two main epithelial cell types of the intestine. Previous studies from our group using an shRNA knockdown approach have shown that YAP1, one of the main Hippo pathway effectors, inhibits the differentiation of these two cell types. In the present study, we show that YAP1 activity is regulated by Src family kinases (SFKs) in these cells. Inhibition of SFKs led to a sharp reduction in YAP1 expression at the protein level, an increase in CDX2 and the P1 forms of HNF4α and of absorptive and goblet cell differentiation specific markers. Interestingly, in Caco-2/15 cells which express both YAP1 and its paralog TAZ, TAZ was not reduced by the inhibition of SFKs and its specific knockdown rather impaired absorptive cell differentiation indicating that YAP1 and TAZ are not always interchangeable for regulating cell functions.

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“…In addition to SF-1, NR4A1 has also been suggested as a transcriptional activator of StAR , CYP11A1 , CYP17A1 , and HSD3β genes ( 21 , 32 ). Although both SF-1 and NR4A1 are important for inducing steroidogenic genes, it is unclear which signaling modulates the activity of SF-1 and NR4A1, respectively, and whether SF-1 and NR4A1 cooperatively regulate steroidogenic gene transcription ( 33 ). In this study, AQ selectively induced NR4A1 activity and increased the expression of NR4A1-mediated steroidogenic enzymes.…”

Section: Discussionmentioning

confidence: 99%

Amodiaquine promotes testosterone production and de novo synthesis of cholesterol and triglycerides in Leydig cells

Choi

Lee

et al. 2021

Journal of Lipid Research

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Testosterone is a hormone essential for male reproductive function. It is produced primarily by Leydig cells in the testicle through activation of steroidogenic acute regulatory protein and a series of steroidogenic enzymes, including a cytochrome P450 side-chain cleavage enzyme (cytochome P450 family 11 subfamily A member 1), 17α-hydroxylase (cytochrome P450 family 17 subfamily A member 1), and 3β-hydroxysteroid dehydrogenase. These steroidogenic enzymes are mainly regulated at the transcriptional level, and their expression is increased by the nuclear receptor 4A1. However, the effect on Leydig cell function of a small molecule-activating ligand, amodiaquine (AQ), is unknown. We found that AQ effectively and significantly increased testosterone production in TM3 and primary Leydig cells through enhanced expression of steroidogenic acute regulatory protein, cytochome P450 family 11 subfamily A member 1, cytochrome P450 family 17 subfamily A member 1, and 3β-hydroxysteroid dehydrogenase. Concurrently, AQ dose-dependently increased the expression of 3-hydroxy-3-methylglutaryl-CoA reductase, a key enzyme in the cholesterol synthesis pathway, through induction of the transcriptional and DNA-binding activities of nuclear receptor 4A1, contributing to increased cholesterol synthesis in Leydig cells. Furthermore, AQ increased the expression of fatty acid synthase and diacylglycerol acyltransferase and potentiated de novo synthesis of fatty acids and triglycerides (TGs). Lipidomics profiling further confirmed a significant elevation of intracellular lipid and TG levels by AQ in Leydig cells. These results demonstrated that AQ effectively promotes testosterone production and de novo synthesis of cholesterol and TG in Leydig cells, indicating that AQ may be beneficial for treating patients with Leydig cell dysfunction and subsequent testosterone deficiency.

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The essential role of TAZ in normal tissue homeostasis

Cited by 13 publications

References 88 publications

TAZ Induces Migration of Microglia and Promotes Neurological Recovery After Spinal Cord Injury

TAZ Induces Migration of Microglia and Promotes Neurological Recovery After Spinal Cord Injury

Src family kinases inhibit differentiation of intestinal epithelial cells through the Hippo effector YAP1

Amodiaquine promotes testosterone production and de novo synthesis of cholesterol and triglycerides in Leydig cells

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