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Cdc42-regulated activin B-induced ADSCs-mediated skin wound healing in vivo.A Representative macroscopic images of wounds treated with PBS, activin B, ADSCs, activin B+ADSCs, ADSCs (Cdc42N17), or activin B+ADSCs (Cdc42N17) on days 0, 3, 7, and 14. B Quantitative analysis of wound closure rate of six mice per group. All values are expressed as mean ± SD from six independent repeats. *P < 0.05
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Background
In our previous study, activin B in combination with ADSCs enhances skin wound healing. However, the underlying molecular mechanisms are not well studied. Cdc42 is recognized to play a critical role in the regulation of stem cells.
Methods
Pull-down assay was performed to investigate the activity of Cdc42. The dominant-negative mutant o...
Citations
... We then performed paired-end sequencing on an IlluminaHiseq4000 (LC Sciences, LLC, Houston, TX, USA), according to the manufacturer's instructions. DEGs were identi ed as previously described [31]. Brie y, DESeq2/EdgeR with Q value ≤ 0.05 was used for the differential expression analysis of RNA-seq data in terms of |log2FC| > 1 and Q value ≤ 0.05 (DESeq2 or EdgeR) or Q value ≤ 0.001 (DEGseq). ...
Fibroblast growth factor 2 (FGF2) is a crucial factor in odontoblast differentiation and dentin matrix deposition, which facilitates pulpodentin repair and regeneration. Nevertheless, the specific biological function of FGF2 in odontoblastic differentiation remains unclear because it is controlled by complex signalling pathways. This study aimed to investigate the mechanism underlying the effect of FGF2 on osteo/odontogenic differentiation of stem cells from the apical papilla (SCAP). SCAP were pretreated with conditioned media containing FGF2 for one week, followed by culturing in induced differentiation medium for another week. RNA sequencing (RNA-seq) combined with quantitative reverse transcription polymerase chain reaction (RT-qPCR) was used to evaluate the pathways affected by FGF2 in SCAP. Osteo/odontogenic differentiation of SCAP was determined using Alizarin red S staining, alkaline phosphatase staining, RT-qPCR, and western blotting. Pretreatment with FGF2 for one week increased the osteo/odontogenic differentiation ability of SCAP. RNA-seq and Kyoto Encyclopedia of Genes and Genomes pathway analyses revealed that phosphatidylinositol 3-kinase (PI3K)/AKT signalling is involved in the osteogenic function of FGF2. RT-qPCR results indicated that SCAP expressed FGF receptors, and western blotting showed that p-AKT was reduced in FGF2-pretreated SCAP. The activation of the PI3K/AKT pathway partially reversed the stimulatory effect of FGF2 on osteo/odontogenic differentiation of SCAP. Our findings suggest that pretreatment with FGF2 enhances the osteo/odontogenic differentiation ability of SCAP by inhibiting the PI3K/AKT pathway.
... Through series studies, Zhang et al. uncovered that activin B/Rho A/mDia1/Cdc42 axis plays a key function in bone marrow-derived mesenchymal stromal cells (BMSCs) migration by promoting membrane ruffling, microtubule morphology, and adhesion signaling dynamics. Inactivation of activin B-Cdc42 inhibits stimulation of Golgi polarization and adipose-derived mesenchymal stem cells-mediated skin wound healing [6][7][8]. Furthermore, overexpressing of activin B was identified in three different models of kidney fibrosis, as well as in human kidneys with fibrosis. Sox9-activin B provides a prospective entry point to surmount kidney fibrosis [9,10]. ...
Background:
Important roles of INHBB in various malignancies are increasingly identified. The underlying mechanisms in gastric cancer (GC) microenvironment are still greatly unexplored.
Methods:
The clinical significance of INHBB and the correlation between INHBB and p-p65 in GC were assessed through analyzing publicly available databases and human paraffin embedded GC tissues. The biological crosstalk of INHBB between GC cells and fibroblasts was explored both in vitro and in vivo. RNA-seq analyses were performed to determine the mechanisms which regulating fibroblasts reprogramming. Luciferase reporter assay and chromatin immunoprecipitation (CHIP) assay were used to verify the binding relationship of p65 and INHBB in GC cells.
Results:
Our study showed that INHBB level was significantly higher in GC, and that increased INHBB was associated with poor survival. INHBB positively regulates the proliferation, migration, and invasion of GC cells in vitro. Also, activin B promotes the occurrence of GC by reprogramming fibroblasts into cancer-associated fibroblasts (CAFs). The high expression of INHBB in GC cells activates the NF-κB pathway of normal gastric fibroblasts by secreting activin B, and promotes fibroblasts proliferation, migration, and invasion. In addition, activin B activates NF-κB pathway by controlling TRAF6 autoubiquitination to induce TAK1 phosphorylation in fibroblasts. Fibroblasts activated by activin B can induce the activation of p65 phosphorylation of GC cells by releasing pro-inflammatory factors IL-1β. p65 can directly bind to the INHBB promoter and increase the INHBB transcription of GC cells, thus establishing a positive regulatory feedback loop to promote the progression of GC.
Conclusions:
GC cells p65/INHBB/activin B and fibroblasts p65/IL-1β signal loop led to the formation of a whole tumor-promoting inflammatory microenvironment, which might be a promising therapeutic target for GC.
Skin aging has been associated with the onset of various skin issues, and recent studies have identified an increase in Cdc42 activity in naturally aging mice. While previous literature has suggested that CASIN, a specific inhibitor of Cdc42 activity, may possess anti‐aging properties, its specific effects on the epidermis and dermis, as well as the underlying mechanisms in naturally aging mice, remain unclear. Our study revealed that CASIN demonstrated the ability to increase epidermal and dermal thickness, enhance dermal‐epidermal junction, and stimulate collagen and elastic fiber synthesis in 9‐, 15‐, and 24‐month‐old C57BL/6 mice in vivo. Moreover, CASIN was found to enhance the proliferation, differentiation, and colony formation and restore the cytoskeletal morphology of primary keratinocytes in naturally aging skin in vitro. Furthermore, the anti‐aging properties of CASIN on primary fibroblasts in aging mice were mediated by the ribosomal protein RPL4 using proteomic sequencing, influencing collagen synthesis and cytoskeletal morphology both in vitro and in vivo. Meanwhile, both subcutaneous injection and topical application exhibited anti‐aging effects for a duration of 21 days. Additionally, CASIN exhibited anti‐inflammatory properties, while reduced expression of RPL4 was associated with increased inflammation in the skin of naturally aging mice. Taken together, our results unveil a novel function of RPL4 in skin aging, providing a foundational basis for future investigations into ribosomal proteins. And CASIN shows promise as a potential anti‐aging agent for naturally aging mouse skin, suggesting potential applications in the field.
