Hhip inhibits proliferation and promotes differentiation of adipocytes through suppressing hedgehog signaling pathway

Wei, Haiyan; Li, Jingjing; Shi, Shengjie; Zhang, Lutong; Xiang, Aoqi; Shi, Xin’e; Yang, Gongshe; Chu, Guiyan

doi:10.1016/j.bbrc.2019.04.047

Cited by 19 publications

(21 citation statements)

References 35 publications

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“…It is therefore unknown whether or not being overweight/obese is associated with plasma Hhip concentrations. Wei et al reported that recombinant Hhip can increase adipocyte differentiation, which results in increased accumulation of lipid droplets in adipocytes by inhibiting the Hh signaling pathway in 3T3-L1 cells, and Hhip messenger RNA expression in adipose tissues was lower in 180-day-old than in 3day-old pigs (13). It was suggested that serum Hhip concentrations may be negatively regulated by differentiated adipose tissues.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, Hhip messenger RNA expression in adipose tissues was higher in 3-day-old than in 180-day-old pigs (13). Recombinant Hhip treatment promoted 3T3-L1 cell differentiation by upregulating the expression of peroxisome proliferatoractivated receptor γ and glucose transporter 4, and downregulating the expression of the Hh signaling transcription factor, Gli1 (13). We previously reported that the Hhip was positively associated with prediabetes and type 2 diabetes (16).…”

Section: Introductionmentioning

confidence: 98%

“…During 8-day adipocyte differentiation, Hhip messenger RNA and protein expressions peaked at day 6 in 3T3-L1 cells (13). In addition, Hhip messenger RNA expression in adipose tissues was higher in 3-day-old than in 180-day-old pigs (13). Recombinant Hhip treatment promoted 3T3-L1 cell differentiation by upregulating the expression of peroxisome proliferatoractivated receptor γ and glucose transporter 4, and downregulating the expression of the Hh signaling transcription factor, Gli1 (13).…”

Section: Introductionmentioning

confidence: 99%

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The Relationship Between Hedgehog-interacting Protein Levels and Obesity: A Case Control Study

Chou

Hung

Lin

et al. 2020

Preprint

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Background Obesity is an independent risk factor for metabolic disorders including diabetes. The Hedgehog-interacting protein (Hhip) is a negative regulator in tissue remodeling, and inhibits the proliferation of adipocytes and promotes their differentiation. In addition, Hhip was positively associated with diabetes. However, relationship between Hhip and obesity in the human body remain unclear. Methods Participants receiving a physical checkup were recruited. Anthropometric and biochemical data were collected. Serum Hhip levels were determined by ELISA. Subjects were classified into normal-weight, overweight, and obese groups based on their body mass index (BMI). The association between Hhip and obesity was examined by a multivariate linear regression analysis.Results In total, 294 subjects who were either of a normal weight (n=166), overweight (n=90), or obese (n=38) were enrolled. Hhip concentrations were 6.51±4.86, 5.79±4.33, and 3.97±3.4 ng/ml in normal-weight, overweight, and obese groups, respectively (p for trend=0.032). Moreover, the regression analysis showed that BMI (β=-0.144, 95% confidence interval (CI)=-0.397~-0.046, p=0.013) was negatively associated with Hhip concentrations after adjusting for sex and age. Being overweight (β=-0.181, 95% CI=-3.311~-0.400, p=0.013) and obese (β=-0.311, 95% CI=-6.393~-2.384, p<0.001) were independently associated with Hhip concentrations after adjusting for sex, age, fasting plasma glucose, the insulin level, and other cardiometabolic risk factors.Conclusions Our results showed that overweight and obese subjects had lower Hhip concentrations than those of a normal weight. Being overweight and obese were negatively associated with Hhip concentrations. Hhip might be a link between obesity and diabetes.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

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The Relationship Between Hedgehog-interacting Protein Levels and Obesity: A Case Control Study

Chou

Hung

Lin

et al. 2020

Preprint

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“…Porcine GCs were cultured in a 6-well culture plate at a density of 4 × 10 5 per well. The cells were treated with miR-214-3p-agomir or antagomir for 48 h. The cells were digested with 0.25% trypsin and terminated with DMEM containing 10% FBS, then collected and fixed in cold 70% ethanol overnight at 4°C [27]. The cells were then washed twice and stained with 50 mg/mL propidium iodide (PI) for 30 min.…”

Section: Flow Cytometrymentioning

confidence: 99%

MiR-214-3p promotes proliferation and inhibits estradiol synthesis in porcine granulosa cells

Shi

Zhou

et al. 2020

J Animal Sci Biotechnol

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Background Granulosa cells (GCs) proliferation and estradiol synthesis significantly affect follicular development. The miR-214-3p expression in the ovarian tissues of high-yielding sows is higher than that in low-yielding sows, indicating that miR-214-3p may be involved in sow fertility. However, the functions and mechanisms of miR-214-3p on GCs are unclear. This study focuses on miR-214-3p in terms of the effects on GCs proliferation and estradiol synthesis. Results Our findings revealed that miR-214-3p promotes proliferation and inhibits estradiol synthesis in porcine GCs. MiR-214-3p can increase the percentage of S-phase cells, the number of EdU labeled positive cells, and cell viability. However, E2 concentration was reduced after miR-214-3p agomir treatment. We also found that miR-214-3p up-regulates the expression of cell cycle genes including cell cycle protein B (Cyclin B), cell cycle protein D (Cyclin D), cell cycle protein E (Cyclin E), and cyclin-dependent kinase 4 (CDK4) at the transcription and translation levels, but down-regulates the mRNA and protein levels of cytochrome P450 family 11 subfamily A member 1 (CYP11A1), cytochrome P450 family 19 subfamily A member 1 (CYP19A1), and steroidogenic acute regulatory protein (StAR) (i.e., the key enzymes in estradiol synthesis). On-line prediction, bioinformatics analysis, a luciferase reporter assay, RT-qPCR, and Western blot results showed that the target genes of miR-214-3p in proliferation and estradiol synthesis are Mfn2 and NR5A1, respectively. Conclusions Our findings suggest that miR-214-3p plays an important role in the functional regulation of porcine GCs and therefore may be a target gene for regulating follicular development.

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“…Porcine GCs were cultured in a 6-well culture plate at a density of 4 × 10 5 per well. The cells were treated with miR-214-3p-agomir or antagomir for 48 h. The cells were digested with 0.25% trypsin and terminated with DMEM containing 10% FBS, then collected and fixed in cold 70% ethanol overnight at 4 ℃ (28). Afterwards, the cells were washed twice and stained with 50 mg/mL propidium iodide (PI) for 30 min.…”

Section: Flow Cytometrymentioning

confidence: 99%

MiR-214-3p Promotes Proliferation and Inhibits Estradiol Synthesis In Porcine Granulosa Cells

Shi

Zhou

et al. 2020

Preprint

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Background: Granulosa cells proliferation and estradiol synthesis significantly affect follicular development. The miR-214-3p expression in the ovarian tissues of high-yielding sows is higher than that in low-yielding sows, indicating that miR-214-3p may be involved in sow fertility. However, the functions and mechanisms of miR-214-3p on granulosa cells are unclear. In this study, miR-214-3p was transfected into porcine ovarian granulosa cells to investigate its functions in terms of proliferation and estradiol synthesis via flow cytometry, CCK-8 assay, EdU staining, ElisA, Real-Time PCR, and Western blot analyses. We also identified the targets of miR-214-3p via Luciferase Reporter Assay. Results: Our findings revealed that miR-214-3p promotes proliferation and inhibits estradiol synthesis in porcine granulosa cells. We also found that miR-214-3p up-regulates the expression of cell cycle genes including Cell cycle protein B (Cyclin B), Cell cycle protein D (Cyclin D), Cell cycle protein E (Cyclin E), and Cyclin-dependent kinase 4 (CDK4) at the transcription and translation levels, while down-regulating the mRNA and protein levels of cytochrome P450 family 11 subfamily A member 1 (CYP11A1), cytochrome P450 family 19 subfamily A member 1 (CYP19A1), and steroidogenic acute regulatory protein (StAR) (i.e., the key enzymes in estradiol synthesis). On-line prediction, bioinformatics analysis, a luciferase reporter assay, RT-qPCR, and Western blot results showed that the target genes of miR-214-3p in proliferation and estradiol synthesis are Mfn2 and NR5A1, respectively. Conclusions: Our findings suggest that miR-214-3p plays an important role in the functional regulation of porcine granulosa cells and therefore may be a target gene for regulating follicular development.

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Hhip inhibits proliferation and promotes differentiation of adipocytes through suppressing hedgehog signaling pathway

Cited by 19 publications

References 35 publications

The Relationship Between Hedgehog-interacting Protein Levels and Obesity: A Case Control Study

The Relationship Between Hedgehog-interacting Protein Levels and Obesity: A Case Control Study

MiR-214-3p promotes proliferation and inhibits estradiol synthesis in porcine granulosa cells

MiR-214-3p Promotes Proliferation and Inhibits Estradiol Synthesis In Porcine Granulosa Cells

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