β1 integrin, ILK and mTOR regulate collagen synthesis in mechanically loaded tendon cells

Abstract

cation products was verified by melting curve analysis. GAPDH was set as a reference, and ΔCt (= Ct Target-Ct GAPDH) values were calculated with Ct mean of each target gene. ΔCt values were plotted and used for statistical analysis. Statistical analysis. The densitometry of immunoblots was evaluated with ImageJ software. The data of densitometry (ratio phospho-protein/vinculin) was analyzed with ANOVA followed by Bonferroni's multiple comparison test or ratio paired T-test. Gene expression data (ΔCt) values were examined by ANOVA followed by Bonferroni's multiple comparison test. The in cell western assay signals were captured using Image Studio Lite (LI-COR, USA) and the data were examined by ANOVA followed by Bonferroni's multiple comparison test. The statistical analyses were carried out using GraphPad Prism. The number of biological replicates is reported in figure captions. P values of less than 0.05 were regarded as statistically significant.

β-Ionone Attenuates Dexamethasone-Induced Suppression of Collagen and Hyaluronic Acid Synthesis in Human Dermal Fibroblasts

“…In an attempt to explore the mechanism underlying the beneficial effects of β-ionone in dexamethasone-induced human dermal fibroblasts, we confirmed that β-ionone suppresses eight dexamethasone-induced GR target genes. Notably, ERRFI1, GILZ, PIK3R1, and DDIT4 have been reported as the negative regulators of PI3K/AKT/mTOR signaling, which can enhance the collagen and hyaluronic acid synthesis [70][71][72][73][74]. SDPR is known to be a calcium-independent phospholipid-binding protein, which is a substrate for protein kinase C (PKC) activation [75].…”

Mechanical Overloading Induced-Activation of mTOR Signaling in Tendon Stem/Progenitor Cells Contributes to Tendinopathy Development

“…Previous studies showed that mechanical stimulation can lead to the activation of the mTOR pathway in human periodontal ligament fibroblasts and human tendon cells ( Blawat et al, 2020 ; Mousavizadeh et al, 2020 ). Research has shown that mTOR signaling may be necessary for an increase in protein synthesis and resulting hypertrophic tissue in response to mechanical loads ( Goodman, 2019 ).…”

“…Previous studies showed that rapamycin, a specific inhibitor of mTOR, suppresses the differentiation of human mesenchymal stem cells and primary mouse bone marrow stromal cells to osteoblasts ( Singha et al, 2008 ; Pantovic et al, 2013 ). A recent study has shown that repetitive mechanical stretching of human tendon cells activates mTOR pathway and increases mRNA translation and collagen synthesis ( Mousavizadeh et al, 2020 ). However, mTOR signaling in TSCs under various mechanical loading conditions remains unclear.…”

Metformin prevents PFKFB3‑related aerobic glycolysis from enhancing collagen synthesis in lung fibroblasts by regulating AMPK/mTOR pathway

“…Briefly, metformin has been shown to directly prohibit respiratory-chain complex 1 of the mitochondrial electron transport chain, resulting in the decrease in adenosine triphosphate (ATP) synthesis and subsequent increased adenosine monophosphate (AMP)/ATP or adenosine diphosphate (ADP)/ATP ratio, leading to AMPK activation by binding to either AMP or ADP (15,16). Mammalian target of rapamycin (mTOR), a downstream target of AMPK, can regulate protein synthesis and cell proliferation via the phosphorylation of eukaryotic translation initiation factor 4E binding protein 1 (4E-BP1) (17)(18)(19). However, enhanced AMPK activity can inhibit rat mesangial cell proliferation and extracellular matrix deposition in high glucose condition with phosphorylation of mTOR and 4E-BP1 (20).…”