Overexpression of transcription factor FOXC2 in cultured human podocytes upregulates injury markers and increases motility

Datta, Neeta; Lindfors, Sonja; Miura, Naoyuki; Saleem, Moin A.; Lehtonen, Sanna

doi:10.1016/j.yexcr.2015.10.035

Cited by 7 publications

(6 citation statements)

References 64 publications

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“…Conditionally immortalized human podocytes (AB8/13) were cultured as described in Datta et al [1] . Differentiated podocytes were serum starved for 12 h in medium supplemented with 1% fetal bovine serum (FBS) and independently treated with 10 ng/ml TNF-α (R&D Systems) for 2–24 h, 4 ng/ml TGF-β (R&D Systems) for 3 or 6 days, 1 μM angiotensin II (Sigma-Aldrich, St. Louis, MO, USA) for 24 h, or 20 mM glucose (Sigma-Aldrich) together with 200 μM palmitate (Sigma-Aldrich) for the last 7 days of the differentiation period.…”

Section: Experimental Design Materials and Methodsmentioning

confidence: 99%

“…FOXC2 was lentivirally overexpressed in differentiated human podocytes as described in Datta et al [1] . The G-actin and F-actin quantification in FOXC2 and control vector-transduced podocytes was performed as described in the G-actin/F-actin in vivo Assay Kit (Cytoskeleton Inc., Denver, CO, USA).…”

Section: Experimental Design Materials and Methodsmentioning

confidence: 99%

“…The article also shows data on the effect of treatments of differentiated podocytes with various factors associated with obesity and diabetes on the expression level of FOXC2. The detailed interpretation of these data and other aspects of podocyte injury mediated by upregulation of FOXC2 can be found in “Overexpression of transcription factor FOXC2 in cultured human podocytes upregulates injury markers and increases motility [1] .…”

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confidence: 99%

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Data supporting the regulation of FOXC2 in podocyte dysfunction

et al. 2016

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This data article shows the expression levels of specific podocyte injury markers and podocyte slit diaphragm protein nephrin in obese and lean Zucker rat glomeruli. It also contains information on the effect of the overexpression of transcription factor FOXC2 on the ratio of F- and G-actin and the expression level of ZO-1 in differentiated human podocytes. The article also shows data on the effect of treatments of differentiated podocytes with various factors associated with obesity and diabetes on the expression level of FOXC2. The detailed interpretation of these data and other aspects of podocyte injury mediated by upregulation of FOXC2 can be found in “Overexpression of transcription factor FOXC2 in cultured human podocytes upregulates injury markers and increases motility [1].

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Section: Experimental Design Materials and Methodsmentioning

confidence: 99%

Section: Experimental Design Materials and Methodsmentioning

confidence: 99%

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confidence: 99%

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Data supporting the regulation of FOXC2 in podocyte dysfunction

et al. 2016

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“…Often, increased expression of FOXC2 during EMT is associated with highly-metastatic cancers [44], some of which can be reduced by shRNA therapy [45]. In podocytes, for instance, increased FOXC2 is associated with increased Vimentin expression, cytoskeletal reorganization, disruption to ZO-1 localization, and increased cell motility [46]. In the current study, cytoskeletal re-organization was noted in hyper-O-GlcNAcylated cells (Figure 3A), and although Vimentin expression was consistent among treatments, ZO-1 expression was reduced by inhibition of OGT (hypo-O-GlcNAcylation, OSMI-1) (Figure 3C).…”

Section: Discussionmentioning

confidence: 99%

Hyper-O-GlcNAcylation promotes epithelial-mesenchymal transition in endometrial cancer cells

Jaskiewicz

Townson

2019

Oncotarget

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Diabetic women have a 2–3 fold increased risk of developing endometrial cancer, however, the molecular aspects of this risk are not fully understood. This study investigated the alteration of cellular O-GlcNAcylation of proteins as the potential mechanistic connection between these two conditions. The endometrial cancer cell line (Ishikawa) was utilized to study the effect of dysregulation of O-GlcNAcylation on epithelial mesenchymal transition (EMT). Hyper-O-GlcNAcylation (via 1 μM Thiamet-G/ThmG or 25 mM Glucose) enhanced the expression of EMT-associated genes ( WNT5B and FOXC2 ), and protein expression of the EMT adhesion molecule, N-Cadherin. Reorganization of stress filaments (actin filaments), consistent with EMT, was also noted in ThmG-treated cells. Interestingly, Hypo-O-GlcNAcylation (via 50 μM OSMI-1) also upregulated WNT5B , inferring that any disruption to O-GlcNAc cycling impacts EMT. However, Hypo-O-GlcNAcylation reduced overall cellular proliferation/migration and the expression of pro-EMT genes ( AHNAK, TGFB2, FGFBP1, CALD1, TFPI2 ). In summary, disruption of O-GlcNAc cycling (i.e., Hyper- or Hypo-O-GlcNAcylation) promoted EMT at both the molecular and cellular levels, but only Hyper-O-GlcNAcylation provoked cellular proliferation/migration, and cytoskeletal reorganization.

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“… 2 Thus, FOXC2 is considered to have an activity to control obesity and insulin resistance. In addition, Datta et al 3 have shown that the overexpression of FOXC2 in human podocyte can cause podocyte function to be impaired and is associated with proteinuria. Some studies suggested that FOXC2 expression is significantly associated with several proteins that are related to insulin resistance (IR), such as PPARγ , UCP-1 , PAI-1 and GLUT4 .…”

Section: Introductionmentioning

confidence: 99%

<p>Effect of Insulin-Regulated FOXC2 Expression in Adipocyte Differentiation and Insulin Resistance</p>

Zhang

Wang

Zuo

et al. 2020

DMSO

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Objective 1) To investigate the effect of FOXC2 on the differentiation of adipose-derived mesenchymal stem cells. 2) To analyze the mechanism between FOXC2 expression regulation in adipose differentiation and insulin resistance (IR). Methods We first amplified the FOXC2 promoter region-512 and cloned it into the luciferase expression vector. The reporter gene system was transfected into the adipose tissue-derived mesenchymal stem cell to study insulin-mediated FOXC2 expression. We also manipulated FOXC2 protein expression by either siRNA or overexpression and studied the differentiation capability of adipose tissue-derived mesenchymal stem cell into adipocytes, as well as the influence on several IR-related genes: GLUT4 , PPARγ , UCP1 and PAI-1 . Results 1) Insulin effectively induced the expression of FOXC2 protein in adipose tissue-derived mesenchymal stem cells under differentiation ( P <0.01). Insulin also induced FOXC2-pro-512T promoter activity significantly ( P <0.01). 2) The stem cell adipose differentiation decreased in the FOXC2 overexpression group. 3) When FOXC2 was overexpressed, the expression of GLUT4 , PAI-1 and UCP1 was higher than control groups ( p <0.001). When FOXC2 was down-regulated by siRNA, both GLUT4 and PAI-1 ’s protein expression were decreased ( p <0.001), and the protein expression of PPARγ was increased ( p <0.001). In the presence of insulin induction, overexpression of FOXC2 led to significantly higher UCP-1 expression ( p <0.001) and lower PAI-1 expression ( p <0.001). The protein expression of GLUT4 , PAI-1 ( p <0.001) and UCP-1 ( p <0.05) was decreased in cells transfected with FOXC2 siRNA. Conclusion Insulin effectively induced the expression of FOXC2 protein in adipose tissue-derived mesenchymal stem cells under differentiation, possibly through the regulation of the FOXC2-pro-512T promoter activity. The different protein expression of FOXC2 has regulatory effects on several genes related to insulin resistance. FOXC2 is an important regulatory factor in adipocyte differentiation and insulin resistance.

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Overexpression of transcription factor FOXC2 in cultured human podocytes upregulates injury markers and increases motility

Cited by 7 publications

References 64 publications

Data supporting the regulation of FOXC2 in podocyte dysfunction

Data supporting the regulation of FOXC2 in podocyte dysfunction

Hyper-O-GlcNAcylation promotes epithelial-mesenchymal transition in endometrial cancer cells

<p>Effect of Insulin-Regulated FOXC2 Expression in Adipocyte Differentiation and Insulin Resistance</p>

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