Aim To explore micro RNAs-integrated pathogenic signaling to control endothelial-mesenchy-mal transition ( EndMT ) in pulmonary hypertension ( PH) by a network bioinformatic approach. Methods Literature-mining method was used to find PH-relat-ed genes and EndMT/EMT-related miRNAs. Bioinfor-matic prediction approach ( DIANA3 , Miranda4 , PicT-ar5 , TargetScan6 , miRDB7 and microT-CDS8 ) was used for miRNA target prediction. Hypergeometric a-nalysis was used to predict miRNAs related to EndMT in PH. The analysis of interactions between PH-rele-vant genes( PH network) was performed with the use of Biological General Repository for Interaction Datasets ( BioGRID ) . These miRNAs were ranked with the highest probability of substantial overlap among their gene targets in the PH-network, the relationship be-tween their targets and the PH functional categories which include hypoxia, inflammation, and transforming growth factor/BMP signaling. Then, the part of results was validated by animal experiment. Lastly the miR-NA-Target network was built using Cytocape 3 . Results List of 230 genes was compiled that were directly im-plicated in the development of PH and 189 miRNAs were related to EndMT in PH. Among 189 miRNAs, only 22 microRNAs(miR-let-7 family, miR-124, miR-130 family, miR-135, miR-144, miR-149, miR-155, miR-16-1, miR-17, miR-181 family, miR-182, miR-200 family, miR-204, miR-205, miR-21, miR-224, miR-27, miR-29 family, miR-301a, miR-31, miR-361 and miR-375) were related to hypoxia, inflamma-tion, and transforming growth factor/BMP signaling. Among these miRNAs, the levels of let-7g, miR-21, miR-124 and miR-130 family were significantly changed in the pulmonary artery in hypoxia-induced PH rats. Conclusions Among numerous miRNAs,22 of which may be involved in hypoxia, inflammation, and transforming growth factor/BMP signaling and re-lated to EndMT in PH by network bioinformatic ap-proach, which provides a theoretical basis for further investigation of EndMT in PH.

To investigate the therapeutic effect and mechanism of Qingfei oral liquid in idiopathic pulmonary fibrosis. Seventy-two male SD rats were divided into control group, model group, pirofenidone group and Qingfei group with 18 animals in each group. The idiopathic pulmonary fibrosis was induced in last three groups by intratracheal injection of bleomycin; pirofenidone group was given oral administration of pirofenidone b.i.d for 21 d, and Qingfei group was given Qingfei oral liquid 3.6 mL/kg q.d for Lung tissues were obtained for HE staining, Masson staining and transforming growth factor (TGF)-β immunohistochemical staining. Superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione (GSH) were detected in tissue homogenates. The BATMAN-TCM database was used to retrieve the chemical components and their corresponding targets of Qingfei oral solution by network pharmacology method, and then the component-target-disease network diagram was constructed. Finally, the pathway enrichment analysis was carried out to explore the molecular mechanism of Qingfei oral liquid against idiopathic fibrosis. Histopathology results showed that Qingfei oral liquid had a similar relieving effect on pulmonary fibrosis as the positive drug pirfenidone; TGF-β secretion had a significant reduction in lung tissues of Qingfei group; and Qingfei oral liquid had better regulatory effect on SOD, MDA and GSH than pirfenidone. The results of component-target-disease network and pathway enrichment analysis showed that the related molecular pathways were concentrated in inflammation, extracellular matrix and cytokines. Qingfei oral liquid has a good therapeutic effect on idiopathic pulmonary fibrosis in rats via regulation of inflammation, extracellular matrix and cytokines.
Animals ; Bleomycin/pharmacology* ; Cytokines ; Drugs, Chinese Herbal ; Glutathione ; Idiopathic Pulmonary Fibrosis/drug therapy* ; Inflammation ; Lung/pathology* ; Male ; Network Pharmacology ; Rats ; Rats, Sprague-Dawley ; Superoxide Dismutase/metabolism* ; Transforming Growth Factor beta/pharmacology*

BACKGROUND: Hair follicles are easily accessible and contain stem cells with different developmental origins, including mesenchymal stem cells (MSCs), that consequently reveal the potential of human hair follicle (hHF)-derived MSCs in repair and regeneration. However, the role of hHF-MSCs in Achilles tendinopathy (AT) remains unclear. The present study investigated the effects of hHF-MSCs on Achilles tendon repair in rabbits. METHODS: First, we extracted and characterized hHF-MSCs. Then, a rabbit tendinopathy model was constructed to analyze the ability of hHF-MSCs to promote repair in vivo . Anatomical observation and pathological and biomechanical analyses were performed to determine the effect of hHF-MSCs on AT, and quantitative real-time polymerase chain reaction, enzyme-linked immunosorbent assay, and immunohistochemical staining were performed to explore the molecular mechanisms through which hHF-MSCs affects AT. Furthermore, statistical analyses were performed using independent sample t test, one-way analysis of variance (ANOVA), and one-way repeated measures multivariate ANOVA as appropriate. RESULTS: Flow cytometry, a trilineage-induced differentiation test, confirmed that hHF-derived stem cells were derived from MSCs. The effect of hHF-MSCs on AT revealed that the Achilles tendon was anatomically healthy, as well as the maximum load carried by the Achilles tendon and hydroxyproline proteomic levels were increased. Moreover, collagen I and III were upregulated in rabbit AT treated with hHF-MSCs (compared with AT group; P  < 0.05). Analysis of the molecular mechanisms revealed that hHF-MSCs promoted collagen fiber regeneration, possibly through Tenascin-C (TNC) upregulation and matrix metalloproteinase (MMP)-9 downregulation. CONCLUSIONS hHF-MSCs can be a treatment modality to promote AT repair in rabbits by upregulating collagen I and III. Further analysis revealed that treatment of AT using hHF-MSCs promoted the regeneration of collagen fiber, possibly because of upregulation of TNC and downregulation of MMP-9, thus suggesting that hHF-MSCs are more promising for AT.
Animals ; Humans ; Rabbits ; Hair Follicle ; Achilles Tendon/pathology* ; Tendinopathy/pathology* ; Proteomics ; Collagen Type I ; Mesenchymal Stem Cells