Transcription Factor 21 Is Required for Branching Morphogenesis and Regulates the Gdnf-Axis in Kidney Development

Ide, Shintaro; Finer, Gal; Maezawa, Yoshiro; Onay, Tuncer; Souma, Tomokazu; Scott, Rizaldy P.; Ide, Kana; Akimoto, Yoshihiro; Li, Chengjin; Ye, Minghao; Zhao, Xiangmin; Baba, Yusuke; Minamizuka, Takuya; Jin, Jing; Takemoto, Minoru; Yokote, Koutaro; Quaggin, Susan E.

doi:10.1681/asn.2017121278

Cited by 27 publications

(29 citation statements)

References 57 publications

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“…During glomerular maturation, the Wilms tumor suppressor gene ( WT1 ) is expressed in the metanephrogenic mesenchyme, which positively regulates Tcf21 , inducing podocyte differentiation ( 36 , 37 ). TCF21 may regulate differentiation through the inhibition of cell cycle arrest-promoting factors in the HEK293 cell line, such as p21, which promotes the expansion of undifferentiated precursor cells and Gdnf-Ret-Wnt1 pathway activation required for mouse branching morphogenesis ( 25 , 38 ).…”

Section: Tcf21 In Kidney Developmentmentioning

confidence: 99%

Role of the bHLH transcription factor TCF21 in development and tumorigenesis

Lotfi

Passaia

Kremer

2021

Braz J Med Biol Res

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Transcription factors control, coordinate, and separate the functions of distinct network modules spatially and temporally. In this review, we focus on the transcription factor 21 (TCF21) network, a highly conserved basic-helix-loop-helix (bHLH) protein that functions to integrate signals and modulate gene expression. We summarize the molecular and biological properties of TCF21 control with an emphasis on molecular and functional TCF21 interactions. We suggest that these interactions serve to modulate the development of different organs at the transcriptional level to maintain growth homeostasis and to influence cell fate. Importantly, TCF21 expression is epigenetically inactivated in different types of human cancers. The epigenetic modification or activation and/or loss of TCF21 expression results in an imbalance in TCF21 signaling, which may lead to tumor initiation and, most likely, to progression and tumor metastasis. This review focuses on research on the roles of TCF21 in development and tumorigenesis systematically considering the physiological and pathological function of TCF21. In addition, we focus on the main molecular bases of its different roles whose importance should be clarified in future research. For this review, PubMed databases and keywords such as TCF21, POD-1, capsulin, tumors, carcinomas, tumorigenesis, development, and mechanism of action were utilized. Articles were selected within a historical context as were a number of citations from journals with relevant impact.

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Section: Tcf21 In Kidney Developmentmentioning

confidence: 99%

Role of the bHLH transcription factor TCF21 in development and tumorigenesis

Lotfi

Passaia

Kremer

2021

Braz J Med Biol Res

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“…Park and associates (22) studied lung cell populations that lineage-labeled for Tcf21, which is a specific marker of white adipose tissue and defines progenitor populations in the heart and kidney (2,8). Lineage labeling at embryonic day (E)11.5, shortly after outpouching of the laryngeo-tracheal groove, which heralds airway branching, identified both peribronchial and vascular smooth muscle cells.…”

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confidence: 99%

The lipofibroblast: more than a lipid-storage depot

McGowan

2019

American Journal of Physiology-Lung Cellular and Molecular Phys

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Lipid-laden cells (initially named lipid-interstitial cells, LIC, and later termed lipofibrobasts, LiF) were first observed in the pulmonary alveolar interstitium of rats and mice during the saccular and alveolar stages of development (7,10). Their location and neutral rather than phospholipid storage granules distinguished them from alveolar type 2 (AT2) epithelial cells and macrophages, and their proliferation kinetics distinguished them from interstitial cells that lacked lipid granules (3). The LiF population peaked during the first two postnatal weeks, when plasma chylomicrons and very-low-density lipoproteins were elevated (3,15). When cultured, the lipid granules dissipated and the cells contained ACTA2 and produced elastin, but lipid storage could be enhanced by exposure to neonatal rat serum or peroxisome proliferator-activated receptor agonists (14, 17). When fibroblasts, which had been isolated in the saccular stage and loaded with [ 3 H]triolein, were cocultured with AT2 cells, the triolein was observed in surfactant lipoproteins, leading to the hypothesis that LiF provide surfactant lipids when alveoli rapidly increase in number (26). Comparable to hepatic stellate cells, LiF store retinyl esters, an endogenous precursor for retinoic acid, which supports elastin synthesis and alveolar formation (16). However, an understanding of the function of LiFs was limited by the transient presence of lipid granules and because the cells lost the granules when cultured.With the development of more sensitive tools to analyze gene expression and proteins in small populations or individual cells, the unique phenotype of LiFs has been defined at a molecular level during alveolarization and during compensatory lung growth after pneumonectomy (1, 6). Signaling by PDGF-A through platelet-derived growth factor receptor-␣ (PDGFR␣) is required for alveolarization, and LiF express PDGFR␣, but their lineage is not directly defined by PDGF-A signaling (25). Lineage-tracing established that sonic hedgehog signaling differentiates fibroblast progenitors to a myofibroblast (MF), ␣-smooth muscle actin (␣SMA)-containing phenotype before postnatal day 2 (P2) when Lif progenitors begin to express the differentiated adipocyte protein perilipin 2 (adipose differentiation-related protein, ADRP), the protein that encapsulates neutral lipid droplets (11,12,21). Myofibroblast differentiation depends on inactivation of a Wnt inhibitory pathway and on sustained sonic hedgehog signaling. Lipofibroblasts are most abundant from P4 to P8 and exhibit other markers of white adipocyte-like differentiation [transcription factor-21 (Tcf21)] and G 0 /G 1 switch protein-2 (GOS2) (18).

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“…Ao et al [ 24 ] reported that TCF21 functions as a corepressor in the ERα signaling pathway and disrupts the growth of ERα-positive breast cancer cells. Ide et al [ 25 ] reported that TCF21 regulates kidney development by activation of the Gdnf-Ret-Wnt11 pathway, which is required for branching morphogenesis. These results, together with our findings, clearly demonstrate that TCF21 modulates multiple biological processes through different signaling pathways.…”

Section: Discussionmentioning

confidence: 99%

Transcription Factor 21 Promotes Chicken Adipocyte Differentiation at Least in Part via Activating MAPK/JNK Signaling

Zhang

Cheng

Jiang

et al. 2021

Genes

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The molecular mechanisms of transcription factor 21 (TCF21) in regulating chicken adipogenesis remain unclear. Thus, the current study was designed to investigate the signaling pathway mediating the effect of TCF21 on chicken adipogenesis. Immortalized chicken preadipocytes cell line (ICP), a preadipocyte cell line stably overexpressing TCF21 (LV-TCF21) and a control preadipocyte cell line (LV-control) were used in the current study. We found that the phosphorylation of c-Jun N-terminal kinases (JNK) was significantly elevated in LV-TCF21 compared to LV-control. After treating ICP cells with a JNK inhibitor SP600125, the differentiation of ICP was inhibited, as evidenced by decreased accumulation of lipid droplets and reduced expression of peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer binding protein α (C/EBPα), adipocyte fatty acid binding protein (A-FABP), and lipoprotein lipase (LPL). Moreover, we found that the inhibition of JNK by SP600125 remarkably impaired the ability of TCF21 to drive adipogenesis. Taken together, our results suggest that TCF21 promotes the differentiation of adipocytes at least in part via activating MAPK/JNK pathway.

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Transcription Factor 21 Is Required for Branching Morphogenesis and Regulates the Gdnf-Axis in Kidney Development

Cited by 27 publications

References 57 publications

Role of the bHLH transcription factor TCF21 in development and tumorigenesis

Role of the bHLH transcription factor TCF21 in development and tumorigenesis

The lipofibroblast: more than a lipid-storage depot

Transcription Factor 21 Promotes Chicken Adipocyte Differentiation at Least in Part via Activating MAPK/JNK Signaling

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