scholarly journals Lats1/2-Mediated Alteration of Hippo Signaling Pathway Regulates the Fate of Bone Marrow-Derived Mesenchymal Stem Cells

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Lang Li ◽  
Liang Dong ◽  
Yifeng Wang ◽  
Xiuhong Zhang ◽  
Jie Yan
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Signaling Pathway ◽  
Vertical Migration ◽  
Transduction Efficiency ◽  
Hippo Signaling ◽  
Migration Assay ◽  
Hippo Signaling Pathway ◽  
Low Expression

Bone marrow-derived mesenchymal stem cells (BMSCs) can be used to enhance lung repair in acute respiratory distress syndrome (ARDS); however, the repairing effect is limited by poor homing and retention of BMSCs. The purpose of this study was to investigate whether Lats1 and Lats2-mediated alteration of Hippo signaling pathway could promote the differentiation, proliferation, and migration of BMSCs. BMSCs were transduced by lentiviral vectors for high and low expression of Lats1 and Lats2. The expression levels of Lats1, Lats2, YAP, and 14-3-3, respectively, were assessed to clarify the regulatory effects of Lats1 and Lats2 on Hippo signaling. Osteogenic (Runx2 and OSX) and adipogenic (C/EBPα and PPAR-γ) transcription factors were determined to clarify the effects of Hippo signaling on BMSCs differentiation. The effects of Hippo signaling on BMSCs proliferation and horizontal and vertical migration were also measured by CCK-8, scratch assay, and Transwell migration assay, respectively. Lentiviral transduction efficiency could reach 93.11%–97.14%. High and low expression of Lats1 and Lats2 could activate and inhibit the Hippo signaling pathway, respectively. High and low expression of Lats1 and Lats2 could inhibit and promote BMSCs differentiation into osteoblasts and adipocytes. High and low expression of Lats1 and Lats2 could inhibit and promote BMSCs proliferation and horizontal and vertical migration, respectively. Our studies suggest that Lats1/2-meidiated inhibition of Hippo signaling in BMSCs may optimize their effects of tissue repair in ARDS, suggesting a novel strategy for enhancing disease therapeutics.

GNAS knockdown suppresses osteogenic differentiation of mesenchymal stem cells via activation of Hippo signaling pathway

2019 ◽  
Vol 234 (12) ◽  
pp. 22299-22310 ◽  
Author(s):  
Jiangdong An ◽  
Guangjie Li ◽  
Jin Zhang ◽  
Haiyu Zhou ◽  
Jin Jiang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Osteogenic Differentiation ◽  
Signaling Pathway ◽  
Hippo Signaling ◽  
Hippo Signaling Pathway

Bone Marrow-Derived Mesenchymal Stem Cells Combined With Simvastatin Accelerates Burn Wound Healing by Activation of the Akt/mTOR Pathway

2020 ◽  
Vol 41 (5) ◽  
pp. 1069-1078
Author(s):  
Parisa Ramhormozi ◽  
Javad Mohajer Ansari ◽  
Sara Simorgh ◽  
Maliheh Nobakht
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Wound Healing ◽  
Mesenchymal Stem Cells ◽  
Combination Therapy ◽  
Signaling Pathway ◽  
Mtor Signaling Pathway ◽  
Burn Wound ◽  
Qrt Pcr ◽  
Burn Wound Healing

Abstract Burn wound healing is one of the most important problems in the field of medical science. Promising results have recently been reported by researchers who used bone marrow mesenchymal stem cells (BMSCs) to treat burn wounds. In this study, we investigated the effects of BMSC therapy in combination with simvastatin (SMV) on angiogenesis as well as on the activity of the Akt/mTOR signaling pathway during burn wound healing in rats. After creating second-degree burn wounds, 40 adult male Wistar rats were randomly divided into four treatment groups: the control, SMV, BMSCs, and the combination therapy group (BMSCs+SMV). Animals were killed 14 days after treatment initiation, and the wounds were removed for histological and molecular analyses. All in all, combination therapy produced better outcomes than individual therapy in terms of the wound closure area, epidermal regeneration level, collagen deposition intensity, and reepithelialization rate. In addition, the elevations of expression levels of Akt and mTOR genes, at both mRNA and protein levels, were more pronounced in the BMSCs+SMV group (P < .05, at least, for both qRT-PCR and western blot assessments). qRT-PCR findings also demonstrated that the wounds treated with the combination of BMSCs and SMV had the highest expression levels of CD31 and VEGF genes (P < .01 for all comparisons). These data suggest that the combined administration of BMSCs transplantation and topical SMV has a great potential in burn wound healing. According to the findings, the beneficial effects of the combination therapy are caused, at least in part, through stimulating Akt/mTOR signaling pathway.

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