PACAP-derived peptide MPAPO impacts Adipose-derived stem cells adipogenic differentiation

Abstract BackgroundRegenerative medicine and tissue engineering have brought new therapeutic prospects to the treatment of soft tissue defects, but the selection of seed cells is the key to treatment. Adipose-derived stem cells (ASCs) have always been a popular candidate for seed cells because of their rich sources, easy access, high plasticity, and strong value-added capabilities. The purpose of the current study is to explore the role of PACAP -derived peptide MPAPO on the adipogenic differentiation of ASCs and its molecular mechanism.MethodsThe effect of MPAPO on the proliferation of adipose-derived stem cells were detected by CCK-8 assay and PI single-staining-flow. To reveal the direct effect of MPAPO on the adipogenic differentiation of ASCs, a model of adipogenic differentiation of adipose stem cells was established. In addition, adipogenic differentiation capacity was assessed using Oil-Red-O Staining, Triglyceride (TG) assay and quantification of gene expression. Finally, the relationship between ASCs adipogenic differentiation and the ERK signaling pathway was explored by Western blot.ResultsMPAPO treatment can significantly promote the proliferation of ASCs. In addition, PACAP treatment improves the adipogenic differentiation efficiency of ASCs, including promoting the accumulation of lipid droplets and triglycerides, and the expression of adipogenic-related transcription factors PPARγ and C/EBPα. The mechanism studies showed that MPAPO selectively binds to the PAC1 receptor to promote the adipogenic differentiation of ASCs via activating the ERK signaling pathway.ConclusionsThe present study shows that MPAPO could promote the adipogenic differentiation of ASCs by activating the ERK signaling pathway, and provide relevant experimental evidence for the filling of clinical tissue defects.

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Taurine Transporter Regulates Adipogenic Differentiation of Human Adipose-Derived Stem Cells through Affecting Wnt/β-catenin Signaling Pathway

International Journal of Biological Sciences ◽

10.7150/ijbs.31794 ◽

2019 ◽

Vol 15 (5) ◽

pp. 1104-1112

Author(s):

Xiaodan Hou ◽

Zhixue Wang ◽

Fang Ding ◽

Yang He ◽

Pengyuan Wang ◽

...

Keyword(s):

Stem Cells ◽

Signaling Pathway ◽

Adipogenic Differentiation ◽

Adipose Derived Stem Cells ◽

Taurine Transporter

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Exosomes Derived From Human Adipose-Derived Stem Cells Inhibit Lipogenesis Involving Hedgehog Signaling Pathway

Frontiers in Bioengineering and Biotechnology ◽

10.3389/fbioe.2021.734810 ◽

2021 ◽

Vol 9 ◽

Author(s):

Ziwan Ji ◽

Zhongming Cai ◽

Shuming Gu ◽

Yucang He ◽

Zikai Zhang ◽

...

Keyword(s):

Stem Cells ◽

Wound Healing ◽

Signaling Pathway ◽

Hedgehog Signaling ◽

Expression Profiles ◽

Adipogenic Differentiation ◽

Clinical Applications ◽

Adipose Derived Stem Cells ◽

High Fat ◽

Hh Signaling

Since obesity impairs wound closure and adipose-derived exosomes (ADEs) regulate wound healing in clinical applications, we hypothesized that ADEs may inhibit adipogenesis of adipose-derived stem cells (ADSCs) to reduce the adverse effects of obesity on wound healing. Hedgehog (Hh) signaling has been previously shown to inhibit adipogenesis in ADSCs. The present study aimed to determine the role of ADEs in the adipogenesis of ADSCs and the Hh signaling pathway. ADSCs collected from human adipose tissues were co-cultured with ADEs and treated with an adipogenic inducer. qRT-PCR showed that ADEs could inhibit adipogenic differentiation of ADSCs and activate Hh signaling. The differences in the mRNA expression profiles of genes related to Hh signaling between the groups that were exposed to either high fat or low fat indicated that increased Hh signaling activation is necessary but not sufficient to inhibit adipogenic differentiation in the ADSC differentiation process. The Hh signaling pathway can be activated effectively by ADEs, especially during high-fat exposure after treatment with ADEs. Oil Red O staining of adipocytes suggested that ADEs inhibited not only adipogenic differentiation, but also lipogenesis in ADSCs. Overall, targeted activation of Hh signaling by ADEs reduced lipid accumulation in ADSCs and may be explored for clinical applications.

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Rg1 promotes the proliferation and adipogenic differentiation of human adipose-derived stem cells via FXR1/Lnc-GAS5-AS1 pathway

Current Stem Cell Research & Therapy ◽

10.2174/1574888x16666211129121414 ◽

2021 ◽

Vol 16 ◽

Author(s):

Fang-Tian Xu ◽

Yin-Li Xu ◽

Yong-Xian Rong ◽

Dong-Lin Huang ◽

Zhong-Hong Lai ◽

...

Keyword(s):

Stem Cells ◽

Regenerative Medicine ◽

Signaling Pathway ◽

Regulatory Network ◽

Transcriptional Regulatory Network ◽

Adipogenic Differentiation ◽

Cell Counting ◽

Adipose Derived Stem Cells ◽

Alizarin Red ◽

Medicine Research

Background: Human adipose-derived stem cells (hASCs) play an important role in regenerative medicine. Objective: Exploring the mechanism of Rg1 in the promotion of the proliferation and adipogenic differentiation of hASCs is important in regenerative medicine research. Methods: In order to observe ginsenoside Rg1 in promoting the proliferation and adipogenic differentiation of hASCs, Rg1 medium at different concentrations was established and tested using the cell counting kit-8 (CCK-8) assay, oil red O staining, alizarin red, and alcian blue. Compared to the control, differentially expressed genes (DEGs) were screened via DEG analysis, which were carried out in the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. To explore the relationship among mRNA, long non-coding RNA (lncRNA) and microRNA (miRNA), we constructed a competing endogenous RNA (ceRNA) network. Results: In this study, Rg1 was observed to promote the proliferation and adipogenic differentiation of hASCs. Additionally, enriched BPs and KEGG pathways may be involved in the promotion process, where FXR1 and Lnc-GAS5-AS1 were found to be regulatory factors. The regulatory network suggested that Rg1 could regulate the adipocytokine signaling pathway and IL−17 signaling pathway via FXR1 and Lnc-GAS5-AS1, which served as the mechanism encompassing the promotion of Rg1 on the proliferation and adipogenic differentiation of hASCs. Conclusion: A comprehensive transcriptional regulatory network related to the promotion ability of Rg1 was constructed, revealing mechanisms regarding Rg1’s promotion of the proliferation and adipogenic differentiation of hASCs. The present study provides a theoretical basis in optimizing the function of hASCs.

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HSPB7 regulates osteogenic differentiation of human adipose derived stem cells via ERK signaling pathway

Stem Cell Research & Therapy ◽

10.1186/s13287-020-01965-4 ◽

2020 ◽

Vol 11 (1) ◽

Author(s):

Chanyuan Jin ◽

Ting Shuai ◽

Zhihui Tang

Keyword(s):

Stem Cells ◽

Heat Shock ◽

Protein Kinase ◽

Heat Shock Protein ◽

Osteogenic Differentiation ◽

Signaling Pathway ◽

Erk Signaling ◽

Adipose Derived Stem Cells ◽

Extracellular Signal

Abstract Background Heat shock protein B7 (HSPB7), which belongs to small heat shock protein family, has been reported to be involved in diverse biological processes and diseases. However, whether HSPB7 regulates osteogenic differentiation of human adipose derived stem cells (hASCs) remains unexplored. Methods The expression level of HSPB7 during the osteogenesis of hASCs was examined by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot analysis. Lentivirus transfection was used to knock down or overexpress HSPB7, which enabled us to investigate the effect of HSPB7 on osteogenic differentiation of hASCs. U0126 and extracellular signal-regulated protein kinase 1/2 (ERK1/2) siRNA were used to identify the mechanism of the HSPB7/ERK1/2 axis in regulating osteogenic differentiation of hASCs. Moreover, ectopic bone formation in nude mice and osteoporosis mice model was used to investigate the effect of HSPB7 on osteogenesis in vivo. Results In this study, we found the expression of HSPB7 was significantly downregulated during the osteogenic differentiation of hASCs. HSPB7 knockdown remarkably promoted osteogenic differentiation of hASCs, while HSPB7 overexpression suppressed osteogenic differentiation of hASCs both in vitro and in vivo. Moreover, we discovered that the enhancing effect of HSPB7 knockdown on osteogenic differentiation was related to the activation of extracellular signal-regulated protein kinase (ERK) signaling pathway. Inhibition of ERK signaling pathway with U0126 or silencing ERK1/2 effectively blocked the stimulation of osteogenic differentiation induced by HSPB7 knockdown. Additionally, we found that HSPB7 expression was markedly increased in mouse bone marrow mesenchymal stem cells (mBMSCs) from the osteoporotic mice which suggested that HSPB7 might be utilized as a potential target in the development of effective therapeutic strategies to treat osteoporosis and other bone diseases. Conclusion Taken together, these findings uncover a previously unrecognized function of HSPB7 in regulating osteogenic differentiation of hASCs, partly via the ERK signaling pathway.

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Deciphering the Emerging Roles of Adipocytes and Adipose-Derived Stem Cells in Fat Transplantation

Cell Transplantation ◽

10.1177/0963689721997799 ◽

2021 ◽

Vol 30 ◽

pp. 096368972199779

Author(s):

Yi Yi ◽

Weijie Hu ◽

Chongru Zhao ◽

Min Wu ◽

Hong Zeng ◽

...

Keyword(s):

Stem Cells ◽

Adipogenic Differentiation ◽

Donor Site ◽

Donor Site Morbidity ◽

Adipose Derived Stem Cells ◽

Multilineage Differentiation ◽

Fat Transplantation ◽

Autologous Fat Transplantation ◽

Essential Components ◽

Tissue Defects

Autologous fat transplantation is widely regarded as an increasingly popular method for augmentation or reshaping applications in soft tissue defects. Although the fat transplantation is of simple applicability, low donor site morbidity and excellent biocompatibility, the clinical unpredictability and high resorption rates of the fat grafts remain an inevitable problem. In the sites of fat transplantation, the most essential components are the adipocyte and adipose-derived stem cells (ADSCs). The survival of adipocytes is the direct factor determining fat retention. The efficacy of fat transplantation is reduced by fat absorption and fibrosis due to the inadequate blood flow, adipocyte apoptosis and fat necrosis. ADSCs, a heterogeneous mixture of cells in adipose tissue, are closely related to tissue survival. ADSCs exhibit the ability of multilineage differentiation and remarkable paracrine activity, which is crucial for graft survival. This article will review the recent existing research on the mechanisms of adipocytes and ADSCs in fat transplantation, especially including adipocyte apoptosis, mature adipocyte dedifferentiation, adipocyte browning, ADSCs adipogenic differentiation and ADSCs angiogenesis. The in-depth understanding of the survival mechanism will be extremely valuable for achieving the desired filling effects.

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