DACH1 regulates cell cycle progression of myeloid cells through the control of cyclin D, Cdk 4/6 and p21

Lee, Jae Woong; Kim, Hyeng-Soo; Kim, Seonggon; Hwang, Junmo; Kim, Young Hun; Lim, Ga Young; Sohn, Wern‐Joo; Yoon, Suk-Ran; Park, Tae Sung; Park, Kwon Moo; Ryoo, Zae Young; Lee, Sanggyu

doi:10.1016/j.bbrc.2012.02.120

Cited by 27 publications

(24 citation statements)

References 21 publications

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“…Therefore, these data suggest that the expression of DACH1 in damaged tubular cells may be mediate cell cycle arrest at G1/S phase or G2/M phase arrest, which contribute to PTC repair. These findings were consistent with our previous work, which demonstrated that DACH1 represses p21 CIP1 and S-phase requires p53-mediated activity [30, 31]. Our previous study also demonstrated that DACH1 inhibited cyclin D1 expression and inversely correlated with PCNA in renal cancer cells [23] or blocked cell proliferation through a c-Jun DNA-binding partner [32].…”

Section: Discussionsupporting

confidence: 92%

Decreased DACH1 expression in glomerulopathy is associated with disease progression and severity

et al. 2016

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Cell fate determination factor dachshund1 (DACH1) is a chromosome-associated protein that regulates cellular differentiation throughout development. Recent genome-wide association studies have show that missense mutation in DACH1 leads to hereditary renal hypodysplasia. Renal DACH1 expression can be used to estimate glomerular filtration rate (eGFR). We firstly characterized the function of DACH1 in normal and diseased renal tissue using immunohistochemistry to assess DACH1 in human renal biopsy specimens from 40 immunoglobulin A nephropathy (IgAN) patients, 20 idiopathic membranous nephropathy (IMN) patients, and 15 minimal change disease (MCD) patients. We found that DACH1 expression was decreased in the nephropathy group relative to healthy controls. DACH1 staining in the glomerulus correlated positively with eGFR (r = 0.41, p < 0.001) but negatively with serum creatinine (r = −0.37, p < 0.01). In vitro, DACH1 overexpression in human podocytes or HK2 cells decreased expression of cyclin D1, but increased expression of p21 and p53, which suggested that DACH1 overexpression in human podocytes or HK2 cells increased the G1/S phase or G2/M cell arrest. Together, These findings indicate that DACH1 expression is decreased in glomerulopathy imply a potential role for DACH1 in the this development of human chornic glomerulopathy. These data suggest that DACH1 is a potential a marker of disease progression and severity for glomerular diseases.

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Section: Discussionsupporting

confidence: 92%

Decreased DACH1 expression in glomerulopathy is associated with disease progression and severity

et al. 2016

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“…In addition, the model makes many predictions of lineage regulators that were not previously associated with those lineages. For example: in S&P cells: HLF; in granulocytes: DACH1, recently reported to regulate cell cycle progression in myeloid cells 18 , BACH1 and NFE2; in macrophages: CREG1; in DCs: ATF6, ETV3, SKIL, NR4A2 and NR4A3, previously shown to be induced in viral infected DCs 19-20 ; in monocytes: POU2F2 (Oct2), previously reported to be up-regulated with macrophage differentiation 21 , and KLF13, a regulator of B and T cells 22 that has a higher expression in monocytes; in B cells: ZFP318; and in NKs: ELF4 (Gm9907), previously shown to control the proliferation and homing of CD8 + T cells 23 . Notably, while this pan-model analysis is useful, it can de-emphasize the contribution of important regulators captured by the model in a more nuanced way, for example as acting only during a limited window of differentiation, but not present in the mature stage.…”

Section: Resultsmentioning

confidence: 99%

Identification of transcriptional regulators in the mouse immune system

et al. 2013

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The differentiation of hematopoietic stem cells into immune cells has been extensively studied in mammals, but the transcriptional circuitry controlling it is still only partially understood. Here, the Immunological Genome Project gene expression profiles across mouse immune lineages allowed us to systematically analyze these circuits. Using a computational algorithm called Ontogenet, we uncovered differentiation-stage specific regulators of mouse hematopoiesis, identifying many known hematopoietic regulators, and 175 new candidate regulators, their target genes, and the cell types in which they act. Among the novel regulators, we highlight the role of ETV5 in γδT cells differntiation. Since the transcriptional program of human and mouse cells is highly conserved1, it is likely that many lessons learned from the mouse model apply to humans.

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“…Previous studies have demonstrated that cyclin D1 and p27 are important in cell proliferation and the cell cycle (20); therefore, their mRNA and protein expression levels were examined in vitro . RT-qPCR revealed that mRNA expression levels of cyclin D1 were significantly reduced by Gal-3 inhibition in hypoxic cells compared with untransfected hypoxic cells (P=0.002; Fig.…”

Section: Resultsmentioning

confidence: 99%

Galectin-3 inhibition ameliorates hypoxia-induced pulmonary artery hypertension

Hao

2016

Molecular Medicine Reports

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Galectin-3 (Gal-3) is a β-galactoside-binding lectin, which is important in inflammation, fibrosis and heart failure. The present study aimed to investigate the role and mechanism of Gal-3 in hypoxia-induced pulmonary arterial hypertension (PAH). Male C57BL/6J and Gal-3−/− mice were exposed to hypoxia, then the right ventricular systolic pressure (RVSP) and Fulton's index were measured, and Gal-3 mRNA and protein expression in the pulmonary arteries was analyzed by reverse transcription-quantitative polymerase chain reaction and western blotting. Compared with the control, hypoxia increased the mRNA and protein expression levels of Gal-3 in wild type murine pulmonary arteries. Gal-3 deletion reduced the hypoxia-induced upregulation of RVSP and Fulton's index. Furthermore, human pulmonary arterial endothelial cells (HPAECs) and human pulmonary arterial smooth muscle cells (HPASMCs) were stimulated by hypoxia in vitro, and Gal-3 expression was inhibited by small interfering RNA. The inflammatory response of HPAECs, and the proliferation and cell cycle distribution of HPASMCs was also analyzed. Gal-3 inhibition alleviated the hypoxia-induced inflammatory response in HPAECs, including tumor necrosis factor-α and interleukin-1 secretion, expression of intercellular adhesion molecule-1 and adhesion of THP-1 monocytes. Gal-3 inhibition also reduced hypoxia-induced proliferation of HPASMCs, partially by reducing cyclin D1 expression and increasing p27 expression. Furthermore, Gal-3 inhibition suppressed HPASMC switching from a ‘contractile’ to a ‘synthetic’ phenotype. In conclusion, Gal-3 serves a fundamental role in hypoxia-induced PAH, and inhibition of Gal-3 may represent a novel therapeutic target for the treatment of hypoxia-induced PAH.

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DACH1 regulates cell cycle progression of myeloid cells through the control of cyclin D, Cdk 4/6 and p21

Cited by 27 publications

References 21 publications

Decreased DACH1 expression in glomerulopathy is associated with disease progression and severity

Decreased DACH1 expression in glomerulopathy is associated with disease progression and severity

Identification of transcriptional regulators in the mouse immune system

Galectin-3 inhibition ameliorates hypoxia-induced pulmonary artery hypertension

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