IFT20 governs mesenchymal stem cell fate through positively regulating TGF-β-Smad2/3-Glut1 signaling mediated glucose metabolism

Li, Yang; Yang, Shuting; Liu, Yang; Qin, Ling

doi:10.1016/j.redox.2022.102373

Cited by 9 publications

(21 citation statements)

References 64 publications

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“…Furthermore, IFT20 may be implicated in the modulation of signaling and cell differentiation of different cell types in addition to those previously described, which include T lymphocytes [ 37 , 53 , 62 , 65 ], proepicardium and myocardium cells [ 72 ], chondrocytes [ 96 ] and osteoblasts [ 83 , 89 ]. Interestingly, it has been recently reported that IFT20 is a critical regulator of bone marrow mesenchymal stem cell (MSC) lineage commitment at an early stage [ 93 ]. MSCs are multipotent stromal cells that can differentiate into a variety of cell types, including chondrocytes, osteoblasts, adipocytes, and myoblasts, and assist postnatal organ growth, repair and regeneration [ 97 , 98 ].…”

Section: Discussionmentioning

confidence: 99%

Section: Cilia-unrelated Vesicular Traffickingmentioning

confidence: 99%

“…Similarly to other cilia-related proteins, including IFT88, IFT20 participates in the maintenance of energy balance by regulating glucose homeostasis ( Figure 3 ) [ 91 , 92 , 93 ]. Interestingly, a significant increase in blood glucose levels and impaired glucose tolerance have been observed in tamoxifen-inducible Ift20 conditional knockout mice where Ift20 was specifically deleted in mesenchymal stem cells (MSCs) at the postnatal stage [ 93 ]. Li and colleagues showed that IFT20 deficiency decreases the expression of genes encoding glycolysis-regulating enzymes, including the glucose transporter Glut1, which is associated with impaired glucose uptake in MSCs.…”

Section: Cilia-unrelated Vesicular Traffickingmentioning

confidence: 99%

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IFT20: An Eclectic Regulator of Cellular Processes beyond Intraflagellar Transport

Finetti

Onnis²,

Baldari³

2022

IJMS

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Initially discovered as the smallest component of the intraflagellar transport (IFT) system, the IFT20 protein has been found to be implicated in several unconventional mechanisms beyond its essential role in the assembly and maintenance of the primary cilium. IFT20 is now considered a key player not only in ciliogenesis but also in vesicular trafficking of membrane receptors and signaling proteins. Moreover, its ability to associate with a wide array of interacting partners in a cell-type specific manner has expanded the function of IFT20 to the regulation of intracellular degradative and secretory pathways. In this review, we will present an overview of the multifaceted role of IFT20 in both ciliated and non-ciliated cells.

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Section: Discussionmentioning

confidence: 99%

Section: Cilia-unrelated Vesicular Traffickingmentioning

confidence: 99%

Section: Cilia-unrelated Vesicular Traffickingmentioning

confidence: 99%

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IFT20: An Eclectic Regulator of Cellular Processes beyond Intraflagellar Transport

Finetti

Onnis²,

Baldari³

2022

IJMS

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“…IFT20 controls the spectral distribution of MSCs during skeletal development by regulating glucose metabolism through activation of TGF-β-Smad2/3 signaling, enhancing the binding activity of Smad2/3 to the glucose transporter 1 (Glut1) promoter, and upregulating Glut1 expression. 120 …”

Section: Molecular Mechanisms Of Metabolic Homeostatic Regulation In ...mentioning

confidence: 99%

Molecular mechanisms of cellular metabolic homeostasis in stem cells

Li,

Jiang,

Wang

2023

Int J Oral Sci

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Many tissues and organ systems have intrinsic regeneration capabilities that are largely driven and maintained by tissue-resident stem cell populations. In recent years, growing evidence has demonstrated that cellular metabolic homeostasis plays a central role in mediating stem cell fate, tissue regeneration, and homeostasis. Thus, a thorough understanding of the mechanisms that regulate metabolic homeostasis in stem cells may contribute to our knowledge on how tissue homeostasis is maintained and provide novel insights for disease management. In this review, we summarize the known relationship between the regulation of metabolic homeostasis and molecular pathways in stem cells. We also discuss potential targets of metabolic homeostasis in disease therapy and describe the current limitations and future directions in the development of these novel therapeutic targets.

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“…Ciliary protein IFT20 is essential for craniofacial skeletal development and bone formation. 19,20 Our previous studies showed that IFT20 governs the fate of mesenchymal stem cells (MSCs) by promoting osteogenesis and inhibiting adipogenesis; 21 deletion of IFT20 in osteoblasts impairs the bone microarchitecture and reduces the bone mass but has no apparent effect on MAT in mice, 21,22 suggesting that IFT20 alone mainly functions in osteogenesis. WWTR1 is a critical fate-determinant factor in MSCs.…”

Section: Introductionmentioning

confidence: 99%

IFT20 and WWTR1 govern bone homeostasis via synchronously regulating the expression and stability of TβRII in osteoblast lineage cells

Yang,

Li,

Yang

2024

Preprint

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Balance of bone and marrow fat formation is critical for bone homeostasis. The imbalance of bone homeostasis will cause various bone diseases, such as osteoporosis. However, the precise mechanisms governing osteoporotic bone loss and marrow adipose tissue (MAT) accumulation remain poorly understood. By analysis of publicly available databases from bone samples of osteoporosis patients, we found that the expression of intraflagellar transport 20 (IFT20) and WW domain containing transcription regulator 1 (WWTR1) were significantly downregulated in osteoblast lineage cells. Additionally, we found that double deletions of IFT20 and WWTR1 in osteoblasts resulted in a significant accumulation of MAT and bone loss. Moreover, IFT20 and WWTR1 deficiency in osteoblasts exacerbated bone-fat imbalance in ovariectomy (OVX)- and high-fat-diet (HFD)-induced osteoporosis mouse models. Mechanistically, we found that deletions of IFT20 and WWTR1 in osteoblasts synergistically inhibited osteogenesis and promoted adipogenesis and osteoclastogenesis. We also found that IFT20 interacted with TGF-β receptor type II (TβRII) to enhance TβRII stability by blocking c-Cbl-mediated ubiquitination and degradation of TβRII. WWTR1 transcriptionally upregulated TβRII expression by directly binding its promoter. These findings indicate that targeting IFT20/WWTR1 may be a potential therapeutic strategy for the treatment of osteoporosis.

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IFT20 governs mesenchymal stem cell fate through positively regulating TGF-β-Smad2/3-Glut1 signaling mediated glucose metabolism

Cited by 9 publications

References 64 publications

IFT20: An Eclectic Regulator of Cellular Processes beyond Intraflagellar Transport

IFT20: An Eclectic Regulator of Cellular Processes beyond Intraflagellar Transport

Molecular mechanisms of cellular metabolic homeostasis in stem cells

IFT20 and WWTR1 govern bone homeostasis via synchronously regulating the expression and stability of TβRII in osteoblast lineage cells

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