scholarly journals Umbilical mesenchymal stem cells attenuates corneal fibrosis induced by fungal keratitis through the TGFβ1/Smad2 signaling pathway

2019 ◽  
Author(s):  
Yue Zhou ◽  
Yuqing Chen ◽  
Suiyue Wang ◽  
Fangyuan Qin ◽  
Wang liya

Abstract Background: Fungal keratitis (FK) is eye microbial infection disease which can leads to severe corneal blindness. Corneal scar formation is one of the major complications of fungal keratitis and is closely related to prognosis. The aim of the current investigation was to evaluate the anti-fibrosis effect of human umbilical cord mesenchymal stem cells (uMSCs) in FK model and further to explore underlying mechanisms. Methods: FK mice model was made by corneal epithelial scratching and F. solani inoculation. The C57BL/6J mice were randomly divided into four groups, including control group, FK group, vehicleinj FK group and uMSCsinj FK group. After injury, antifungal drug natamycin eye drops were used topically to FK mice eyes 6 times per day for 7 days to inhibit fungi growth. Mice received repeated subconjunctival injection of uMSCs or veichle for 3 times including the 1d, 4d and 7d after wounding. At 14d, 21d and 28d post-injury, clinical observation, histological examination, second harmonic generation, immunofluoresence staining and molecular assays were performed. Results: The uMSCs topical administration reduced corneal scar formation and corneal opacity, accompanying with decreased corneal thickness and inflammatory cell infiltration, following down-regulated fibrotic-related factors α-SMA, TGFβ1, CTGF, and COLⅠ and finally inhibited phosphorylation of TGFβ1/Smad2 signaling pathway, which indicating the potential anti-fibrotic and protective effect of human uMSCs against FK-induced corneal fibrosis. Conclusion: Human uMSCs can evidently inhibit corneal fibrosis after FK wounding through TGFβ1/Smad2 signaling pathway regulation. Keywords: Fungal keratitis, corneal fibrosis, umbilical cord mesenchymal stem cells

2021 ◽  
Author(s):  
Tianqin Xie ◽  
Qiming Huang ◽  
Qiulang Huang ◽  
Haixia Zeng ◽  
Jianping Liu

Abstract ObjectiveIn recent years, cell therapy has become a new research direction in the treatment of diabetes. However, the underlying molecular mechanisms of mesenchymal stem cells (MSCs) participate in such treatment has not been clarified. MethodsIn this study, human umbilical cord mesenchymal stem cells (HUC-MSCs) isolated from newborns were progressively induced into insulin-producing cells (IPCs) using small molecules. HUC-MSCs (S0) and four induced stage (S1-S4) samples were prepared. We then performed transcriptome sequencing experiments to obtain the dynamic expression profiles of both mRNAs and long noncoding RNAs (lncRNAs). ResultsWe found that the number of differentially expressed lncRNAs and mRNAs showed a decreasing trend during differentiation. Gene Ontology (GO) analysis showed that the target genes of differentially expressed lncRNAs were associated with translation, cell adhesion, and cell connection. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that the NF-KB signaling pathway, MAPK signaling pathway, HIPPO signaling pathway, PI3K-Akt signaling pathway, and p53 signaling pathway were enriched in these differentially expressed lncRNA-targeting genes. We also found that the coexpression of the lncRNA: CTBP1-AS2 with the PROX1, and the lncRNAs AC009014.3 and GS1-72M22.1 with the mRNA JARID2 was related to the development of pancreatic beta cells. Moreover, the coexpression of the lncRNAs :XLOC_ 050969, LINC00883, XLOC_050981, XLOC_050925, MAP3K14- AS1, RP11-148K1.12, and CTD2020K17.3 with p53, regulated insulin secretion by pancreatic beta cells.ConclusionThis research revealed that HUC-MSCs combined with small molecule compounds were successfully induced into IPCs. Differentially expressed lncRNAs may regulate the insulin secretion of pancreatic beta cells by regulating multiple signaling pathways. The lncRNAs: AC009014.3,Gs1-72m21.1 and CTBP1-AS2 may be involved in the development of pancreatic beta cells, and the lncRNAs: XLOC_050969, LINC00883, XLOC_050981, XLOC_050925, MAP3K14-AS1, RP11-148K1.12, and CTD2020K17.3 may be involved in regulating the insulin secretion of pancreatic beta cells, thus providing a lncRNA catalog for future research regarding the mechanism of the transdifferentiation of HUC-MSCs into IPCs. It also provides a new theoretical basis for the transplantation of insulin-producing cells into diabetic patients in the future.


2021 ◽  
Author(s):  
Shi-wei Ren ◽  
Yang Song ◽  
Qing-run Zhu ◽  
Min-gang He ◽  
Jie Qiu ◽  
...  

Abstract BackgroundPostmenopausal osteoporosis (PMO) is a relatively common disease characterized by low bone mass and microstructural changes of trabecular bone. The reduced bone strength is caused a variety of complications, including fragility fracture and sarcopenia.MethodsWe used CCK-8 and EdU assays to evaluate cell proliferation rates. The osteogenesis effect was detected using ALP staining, alizarin red staining, and q-PCR. In vivo, the effects of exosomes derived from HUC-MSCs were evaluated using HE staining, IHC staining and Masson staining. In addition, we explored the mechanism of exosomes and found that the AKT signaling pathway played an important role in osteogenesis and cell proliferation.ResultsThis paper mainly explored the function of exosomes derived from human umbilical cord mesenchymal stem cells (HUC-MSCs) and provided a new strategy for the treatment of postmenopausal osteoporosis. ConclusionsIn conclusion, exogenous administration of exosomes can contribute to the treatment postmenopausal osteoporosis to a certain extent.


Bioengineered ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 1986-1996
Author(s):  
Lijun Kong ◽  
Xiangxiang Xu ◽  
Hewei Zhang ◽  
Yi Zhou ◽  
Hongjian Huang ◽  
...  

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