scholarly journals Porcine bone collagen peptides promote osteoblast proliferation and differentiation by activating the PI3K/Akt signaling pathway

2020 ◽  
Vol 64 ◽  
pp. 103697 ◽  
Author(s):  
Lingyu Zhu ◽  
Yingying Xie ◽  
Boting Wen ◽  
Mengliang Ye ◽  
Yusi Liu ◽  
...  
2021 ◽  
Vol 12 (2) ◽  
Author(s):  
Xuemei Shen ◽  
Jia Tang ◽  
Rui Jiang ◽  
Xiaogang Wang ◽  
Zhaoxin Yang ◽  
...  

AbstractMany novel non-coding RNAs, such as microRNAs (miRNAs) and circular RNAs (circRNAs), are involved in various physiological and pathological processes. The PI3K/AKT signaling pathway is important for its role in regulating skeletal muscle development. In this study, molecular and biochemical assays were used to confirm the role of miRNA-145 (miR-145) in myoblast proliferation and apoptosis. Based on sequencing data and bioinformatics analysis, we identified a new circRILPL1, which acts as a sponge for miR-145. The interactions between circRILPL1 and miR-145 were examined by bioinformatics, a luciferase assay, and RNA immunoprecipitation. Mechanistically, knockdown or exogenous expression of circRILPL1 in the primary myoblasts was performed to prove the functional significance of circRILPL1. We investigated the inhibitory effect of miR-145 on myoblast proliferation by targeting IGF1R to regulate the PI3K/AKT signaling pathway. A novel circRILPL1 was identified that could sponge miR-145 and is related to AKT activation. In addition, circRILPL1 was positively correlated with muscle proliferation and differentiation in vitro and could inhibit cell apoptosis. The newly identified circRILPL1 functions as a miR-145 sponge to regulate the IGF1R gene and rescue the inhibitory effect of miR-145 on the PI3K/AKT signaling pathway, thereby promoting myoblast growth.


2021 ◽  
Vol 23 (1) ◽  
pp. 115
Author(s):  
Ming Lyu ◽  
Xu Wang ◽  
Xiangyu Meng ◽  
Hongrun Qian ◽  
Qian Li ◽  
...  

MicroRNAs (miRNAs) are endogenously expressed small noncoding RNAs and play critical roles in the regulation of post-transcriptional gene expression. Our previous study uncovered that chi-miR-487b-3p is widespread in different goat tissues, which is significantly higher in muscle, especially in lamb. Here, we demonstrate the role of chi-miR-487b-3p as a myogenic miRNA that regulates skeletal muscle development. chi-miR-487b-3p overexpression was demonstrated to significantly inhibit goat myoblast proliferation and differentiation, whereas chi-miR-487b-3p inhibition resulted in the opposite effects. Next, chi-miR-487b-3p was predicted to target the 3′UTR of insulin receptor substrate 1 (IRS1) gene by Target-Scan and miRDB. The results of dual-luciferase assay, RT-qPCR, and western blot all confirmed that IRS1 might be a direct target of chi-miR-487b-3p as its expression was negatively regulated by chi-miR-487b-3p. siRNA silencing of IRS1 further demonstrated significant inhibition on goat myoblast proliferation and differentiation, confirming the effect of IRS1 downregulation by chi-miR-487b-3p in myogenesis. In addition, chi-miR-487b-3p knockout goat myoblast clones were generated using CRISPR/Cas9 technology, and we further illustrated that chi-miR-487b-3p regulates goat myoblast growth through the PI3K/Akt signaling pathway by targeting IRS1. Collectively, our work demonstrated that chi-miR-487b-3p is a potent inhibitor of skeletal myogenesis and provided new insights into the mechanisms of miRNA on the regulation of goat growth.


Dermatology ◽  
2021 ◽  
pp. 1-9
Author(s):  
Nannan Liang ◽  
Wenjuan Chang ◽  
Aihong Peng ◽  
Yue Cao ◽  
Junqin Li ◽  
...  

<b><i>Background:</i></b> Psoriasis is a chronic inflammatory skin disease characterized by excessive proliferation and abnormal differentiation of keratinocytes. Dermal mesenchymal stem cells (DMSCs) are not only involved in the regeneration of skin tissue, but also can regulate skin microenvironment by secreting cytokines. However, whether and how psoriatic DMSCs regulate proliferation and differentiation of keratinocytes remains unknown. <b><i>Objective:</i></b> To study the effects of psoriatic DMSCs on the proliferation, differentiation, and migration of keratinocytes and the underlying mechanisms. <b><i>Methods:</i></b> Following co-cultures of HaCaT cells with either psoriatic DMSCs (p-DMSCs) or DMSCs from normal volunteers (n-DMSCs), HaCaT cell proliferation was assessed using CCK-8 and EDU incorporation assay, while scratch assay and transwell assay were used to assess cell migration. qRT-PCR was used to determine expression levels of mRNA for cell proliferation (Ki-67) and differentiation (keratin 5, involucrin, and filaggrin). Western blot was used to measure expression levels of proteins associated with keratinocyte proliferation and differentiation in cultured HaCaT cells treated with or without PI3K inhibitor. ELISA assay was used to measure expression profile of stem cell factor (SCF), epidermal growth factor (EGF), and interleukin-11 (IL-11) within the co-culture supernatants. <b><i>Results:</i></b> The results showed that p-DMSCs displayed a higher potency than n-DMSCs in stimulating proliferation, differentiation, and migration of HaCaT cells. Expression levels of PI3K and AKT proteins were markedly increased in HaCaT cells co-cultured with DMSCs versus HaCaT cell culture alone. Moreover, inhibition of the PI3K/AKT signaling pathway reversed the effect of p-DMSCs on proliferation, differentiation, and migration of HaCaT cells. Compared with n-DMSCs, the p-DMSCs showed increased secretion of IL-11, EGF, and SCF. <b><i>Conclusion:</i></b> p-DMSCs stimulate HaCaT cell proliferation, differentiation and migration via activating the PI3K/AKT signaling pathway, providing a new insight into the pathogenesis of psoriasis.


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