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FGF2-induced PI3K/Akt signaling evokes greater proliferation and adipogenic differentiation of human adipose stem cells from breast than from abdomen or thigh.

ABSTRACT: In this study, human adipose stem cells were isolated from subcutaneous fat in the thigh (htASCs), abdomen (haASCs) and breast (hbASCs). Flow cytometry was used to detect cell surface markers, and an enzyme-linked immunosorbent assay was used to detect paracrine activity. Paracrine gene expression in the three cell types was examined using real-time qPCR, and adipogenic ability was assessed using Oil Red O staining. RNA from third-passage haASCs and hbASCs was sequenced. The results showed that the differentiation potential marker markers CD49d and CD54 were similar across hbASCs from 10 subjects. The hbASCs showed higher colony forming ability and expression of fibroblast growth factor-2, tissue inhibitor of metalloproteinase-1 and stromal cell derived factor-1 than htASCs and haASCs. Stimulating hbASCs with FGF2 promoted adipogenic differentiation, while treating the cells with the PI3K inhibitor LY294002 inhibited differentiation. These results suggest that the PI3K/Akt signaling pathway can promote proliferation and adipogenic differentiation of adipose stem cells, and that activation of this pathway by FGF2 may explain why hbASCs show greater proliferation and adipogenic differentiation than haASCs and htASCs.

SUBMITTER: Lu GM

PROVIDER: S-EPMC7425436 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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FGF2-induced PI3K/Akt signaling evokes greater proliferation and adipogenic differentiation of human adipose stem cells from breast than from abdomen or thigh.

Lu Guan-Ming GM Rong Yong-Xian YX Liang Zhi-Jie ZJ Hunag Dong-Lin DL Wu Fang-Xiao FX Ma Yan-Fei YF Luo Zhi-Zhai ZZ Liu Xin-Heng XH Mo Steven S Li Hong-Mian HM

Aging 20200724 14

In this study, human adipose stem cells were isolated from subcutaneous fat in the thigh (htASCs), abdomen (haASCs) and breast (hbASCs). Flow cytometry was used to detect cell surface markers, and an enzyme-linked immunosorbent assay was used to detect paracrine activity. Paracrine gene expression in the three cell types was examined using real-time qPCR, and adipogenic ability was assessed using Oil Red O staining. RNA from third-passage haASCs and hbASCs was sequenced. The results showed that ...[more]

PMID: 32706337

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Project description:ContextThe expression of adipogenic genes in sc adipose tissue has been reported to be lower among patients with HIV-associated lipoatrophy than HIV-uninfected controls. It is unclear whether this is a result or cause of lipoatrophy.ObjectiveThe objective of the study was to investigate the temporal relationships among changes in adipogenic gene expression in sc adipose tissue and changes in body fat distribution and metabolic complications in HIV-infected subjects on antiretroviral therapy.DesignThis was a prospective longitudinal study.SettingThe study was conducted at HIV clinics in Seattle, Washington.ParticipantsThe study population included 31 HIV-infected and 12 control subjects.InterventionsSubjects were followed up for 12 months after they initiated or modified their existing antiretroviral regimen.Main outcome measuresChanges in body composition, plasma lipids, insulin sensitivity, and gene expression in sc abdominal and thigh adipose tissue.ResultsSubjects who developed lipoatrophy (n=10) had elevated fasting triglycerides [3.16 (sd 2.79) mmol/liter] and reduced insulin sensitivity as measured by frequently sampled iv glucose tolerance test [1.89 (sd 1.27)x10(-4) min(-1)/microU.ml] after 12 months, whereas those without lipoatrophy (n=21) did not show any metabolic complications [triglycerides 1.32 (sd 0.58) mmol/liter, P=0.01 vs. lipoatrophy; insulin sensitivity 3.52 (sd 1.91)x10(-4) min(-1)/microU.ml, P=0.01 vs. lipoatrophy]. In subjects developing lipoatrophy, the expression of genes involved in adipocyte differentiation, lipid uptake, and local cortisol production in thigh adipose tissue was significantly reduced already at the 2-month visit, several months before any loss of extremity fat mass was evident.ConclusionsIn HIV-infected subjects, lipoatrophy is associated with elevated fasting triglycerides and insulin resistance and might be caused by a direct or indirect effect of antiretroviral drugs on sc adipocyte differentiation.

Project description:BackgroundCircular RNAs (circRNAs) are involved in diverse processes that drive cancer development. However, the expression landscape and mechanistic function of circRNAs in osteosarcoma (OS) remain to be studied.MethodsBioinformatic analysis and high-throughput RNA sequencing tools were employed to identify differentially expressed circRNAs between OS and adjacent noncancerous tissues. The expression level of circ_001422 in clinical specimens and cell lines was measured using qRT-PCR. The association of circ_001422 expression with the clinicopathologic features of 55 recruited patients with OS was analyzed. Loss- and gain-of-function experiments were conducted to explore the role of circ_001422 in OS cells. RNA immunoprecipitation, fluorescence in situ hybridization, bioinformatics database analysis, RNA pulldown assays, dual-luciferase reporter assays, mRNA sequencing, and rescue experiments were conducted to decipher the competitive endogenous RNA regulatory network controlled by circ_001422.ResultsWe characterized a novel and abundant circRNA, circ_001422, that promoted OS progression. Circ_001422 expression was dramatically increased in OS cell lines and tissues compared with noncancerous samples. Higher circ_001422 expression correlated with more advanced clinical stage, larger tumor size, higher incidence of distant metastases and poorer overall survival in OS patients. Circ_001422 knockdown markedly repressed the proliferation and metastasis and promoted the apoptosis of OS cells in vivo and in vitro, whereas circ_001422 overexpression exerted the opposite effects. Mechanistically, competitive interactions between circ_001422 and miR-195-5p elevated FGF2 expression while also initiating PI3K/Akt signaling. These events enhanced the malignant characteristics of OS cells.ConclusionsCirc_001422 accelerates OS tumorigenesis and metastasis by modulating the miR-195-5p/FGF2/PI3K/Akt axis, implying that circ_001422 can be therapeutically targeted to treat OS.

Dataset Information

FGF2-induced PI3K/Akt signaling evokes greater proliferation and adipogenic differentiation of human adipose stem cells from breast than from abdomen or thigh.

Publications

FGF2-induced PI3K/Akt signaling evokes greater proliferation and adipogenic differentiation of human adipose stem cells from breast than from abdomen or thigh.

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