Mohawk Promotes the Tenogenesis of Mesenchymal Stem Cells Through Activation of the TGF beta Signaling Pathway
STEM CELLS
Authors: Liu, Huanhuan; Zhang, Can; Zhu, Shouan; Lu, Ping; Zhu, Ting; Gong, Xiaonan; Zhang, Ziwang; Hu, Jiajie; Yin, Zi; Heng, Boon Chin; Chen, Xiao; Ouyang, Hong Wei
Abstract
The transcription factor Mohawk (Mkx) is expressed in developing tendons and is an important regulator of tenogenic differentiation. However, the exact roles of Mkx in tendinopathy and tendon repair remain unclear. Using gene expression Omnibus datasets and immunofluorescence assays, we found that Mkx expression level was dramatically lower in human tendinopathy tissue and it is activated at specific stages of tendon development. In mesenchymal stem cells (MSCs), ectopic Mkx expression strikingly promoted tenogenesis more efficiently than Scleraxis (Scx), a well-known master transcription factor of tendon. Significantly higher levels of tenogenic gene expression and collagen fibril growth were observed with Mkx versus Scx. Interestingly, it was observed that Mkx dramatically upregulated Scx through binding to the Tgfb2 promoter. Additionally, the transplantation of Mkx-expressing-MSC sheets promoted tendon repair in a mouse model of Achilles-tendon defect. Taken together, these data shed light on previously unrecognized roles of Mkx in tendinopathy, tenogenesis, and tendon repair as well as in regulating the TGF beta pathway.
Construction and Investigation of MicroRNA-mRNA Regulatory Network of Gastric Cancer with Helicobacter pylori Infection
BIOCHEMISTRY RESEARCH INTERNATIONAL
Authors: Yang, Ping; Liu, Junjie; Yang, Tianci; Zhang, Lei; Gong, Peiyou; Li, Boqing; Zhou, Xiuzhi
Abstract
Background. Helicobacter pylori (H. pylori) is a common human pathogen, which is closely correlated with gastric cancer (GC). However, the mechanism of H. pylori-related GC has not been elucidated. This study aimed to explore the role of H. pylori infection in GC and find biomarkers for early diagnosis of H. pylori-related GC. Methods. We identified differentially expressed microRNAs (DEMs) and genes (DEGs) from the Gene Expression Omnibus (GEO) dataset, constructed microRNA-(miRNA-) mRNA expression networks, analyzed the function and signal pathway of cross-genes, analyzed the relations between cross-genes and GC prognosis with the Cancer Genome Atlas (TCGA) data, and verified the expression of cross-genes in patients with H. pylori infection. Results. 22 DEMs and 68 DEGs were identified in GSE197694 and GSE27411 dataset. 16 miRNAs and 509 genes were involved in the expression network, while the cross-genes of the network were mainly enriched in MAP kinase (MAPK) signaling pathway and TGF-beta signaling pathway. Patients with higher expression of hsa-miR-196b-3p, CALML4, or SMAD6 or lower expression of PITX2 or TGFB2 had better outcomes than those with lower expression of hsa-miR-196b-3p, CALML4, or SMAD6 or higher expression of PITX2 or TGFB2 (P < 0.05). Patients with H. pylori infection had a higher expression of hsa-miR-196b-3p and CALML4 than those without H. pylori infection (P < 0.05). Conclusion. The study of miRNA-mRNA expression network would provide molecular support for early diagnosis and treatment of H. pylori-related GC.