The scientific basis of acupuncture on mesenchymal stem cells (MSCs) for treating ischemic stroke (IS) is discussed. MSCs transplantation has great potential for the treatment of tissue damage caused by early stage inflammatory cascade reactions of IS, but its actual transformation is limited by various factors. How to improve the homing efficiency of MSCs is the primary issue to enhance its efficacy. As such, the possible mechanisms of acupuncture and MSCs transplantation in inhibiting inflammatory cascade reactions induced by IS are explored by reviewing literature, and a hypothesis that acupuncture could promote the secretion of stromal cell-derived factor-1α (SDF-1α) from ischemic foci to regulate SDF-1α/CXC chemokine receptor 4 (CXCR4) axis, thereby improving the homing efficiency of MSCs transplantation, exerting its neuroprotective function, and improving the bed transformation ability, is proposed.
Humans ; Ischemic Stroke ; Chemokine CXCL12 ; Acupuncture Therapy ; Mesenchymal Stem Cells ; Inflammation

OBJECTIVES: This study aimed to investigate how naringenin (Nar) affected the anti-inflammatory, vascula-rization, and osteogenesis differentiation of human periodontal ligament stem cells (hPDLSCs) stimulated by lipopolysaccharide (LPS) and to preliminarily explore the underlying mechanism. METHODS: Cell-counting kit-8 (CCK8), cell scratch test, and Transwell assay were used to investigate the proliferation and migratory capabilities of hPDLSCs. Alkaline phosphatase (ALP) staining, alizarin red staining, lumen-formation assay, enzyme-linked immunosorbent assay, quantitative timed polymerase chain reaction, and Western blot were used to measure the expression of osteopontin (OPN), Runt-related transcription factor 2 (RUNX2), vascular endothlial growth factor (VEGF), basic fibroblast growth factor (bFGF), von Willebrand factor (vWF), tumor necrosis factor-α (TNF-α), and interleukin (IL)-6. RESULTS: We observed that 10 μmol/L Nar could attenuate the inflammatory response of hPDLSCs stimulated by 10 μg/mL LPS and promoted their proliferation, migration, and vascularization differentiation. Furthermore, 0.1 μmol/L Nar could effectively restore the osteogenic differentiation of inflammatory hPDLSCs. The effects of Nar's anti-inflammatory and promotion of osteogenic differentiation significantly decreased and inflammatory vascularization differentiation increased after adding AMD3100 (a specific CXCR4 inhibitor). CONCLUSIONS Nar demonstrated the ability to promote the anti-inflammatory, vascularization, and osteogenic effects of hPDLSCs stimulated by LPS, and the ability was associated with the stromal cell-derived factor/C-X-C motif chemokine receptor 4 signaling axis.
Humans ; Anti-Inflammatory Agents/pharmacology* ; Cell Differentiation ; Cell Proliferation ; Cells, Cultured ; Chemokine CXCL12 ; Lipopolysaccharides/pharmacology* ; Osteogenesis ; Periodontal Ligament/metabolism* ; Receptors, Chemokine/metabolism* ; Stem Cells ; Interleukin-8/metabolism*

OBJECTIVE: To investigate the regulatory effects of miR-30e-5p on biological behaviors of colorectal cancer cells and the role of PTEN/CXCL12 axis in mediating these effects. METHODS: Bioinformatic analysis was performed to explore the differential expression of miR-30e-5p between colorectal cancer tissues and normal tissues. RT-qPCR was used to detect the differential expression of miR-30e-5p in intestinal epithelial cells and colorectal cancer cells. Bioinformatics and dual luciferase assay were used to predict and validate the targeting relationship between miR-30e-5p and PTEN. Human and murine colorectal cancer cell lines were transfected with miR-30e-5p mimics, miR-30e-5p inhibitor, miR-30e-5p mimics+LV-PTEN, or miR-30e-5p inhibitor + si-PTEN. The changes in biological behaviors of the cells were detected using plate clone formation assay, CCK-8 assay, flow cytometry, scratch healing and Transwell assays. PTEN and CXCL12 expressions in the cancer cells were detected by Western blotting. The effects of miR-30e-5p inhibitor on colorectal carcinogenesis and development were observed in nude mice. RESULTS: Bioinformatic analysis showed that miR-30e-5p expression was significantly elevated in colorectal cancer tissues compared with the adjacent tissue (P < 0.01). Higher miR-30e-5p expression was detected in colorectal cancer cell lines than in intestinal epithelial cells (P < 0.01). Dual luciferase assay confirmed the targeting relationship between miR-30e-5p and PTEN (P < 0.05). Transfection with miR-30e-5p mimics significantly enhanced proliferation and metastasis and inhibited apoptosis of the colorectal cancer cells (P < 0.05), and co-transfection with LV-PTEN obviously reversed these changes (P < 0.05). MiR-30e-5p mimics significantly inhibited PTEN expression and enhanced CXCL12 expression in the cancer cells (P < 0.01), and miR-30e-5p inhibitor produced the opposite effect. Transfection with miR-30e-5p inhibitor caused cell cycle arrest in the cancer cells, which was reversed by co-transfection with si-PTEN (P < 0.05). In the in vivo experiments, the colorectal cancer cells transfected with miR-30e-5p inhibitor showed significantly lowered tumorigenesis. CONCLUSION Overexpression of miR-30e-5p promotes the malignant behaviors of colorectal cancer cells by downregulating PTEN to activate the CXCL12 axis.
Humans ; Animals ; Mice ; MicroRNAs/metabolism* ; Cell Line, Tumor ; Cell Proliferation/physiology* ; Mice, Nude ; Cell Movement/physiology* ; Colorectal Neoplasms/pathology* ; Luciferases/metabolism* ; Gene Expression Regulation, Neoplastic ; PTEN Phosphohydrolase/metabolism* ; Chemokine CXCL12/metabolism*

Pulmonary fibrosis is an irreversible interstitial lung disease characterized by lung parenchyma remodeling and collagen deposition. In recent years, the incidence and mortality of pulmonary fibrosis caused by unknown causes have risen. However, its pathogenesis is still unclear. C-X-C motif chemokine ligand 12 (CXCL12)/C-X-C chemokine receptor 4 (CXCR4)/CXCR7 signal axis plays a critical regulatory role in pulmonary fibrosis disease. In addition, the signal axis has been shown to regulate recruitment and migration of circulating fibrocytes, mesenchymal stem cells to the damage lung tissue, the migration of endothelial cells, the proliferation and differentiation of fibroblasts and endothelial cells, which further affects the occurrence and progression of pulmonary fibrosis. In this review, we summarized the pathogenesis and treatment research progress of CXCL12 and its receptor CXCR4/CXCR7 in the occurrence and progression of pulmonary fibrosis.
Chemokine CXCL12 ; Endothelial Cells/pathology* ; Humans ; Ligands ; Lung/pathology* ; Pulmonary Fibrosis/pathology* ; Receptors, CXCR4

OBJECTIVE: To investigate whether miR-372-5p regulates PI3K/AKT/CXCL12 signaling pathway by targeting PTEN to promote metastasis of colorectal cancer cells. METHODS: We detected the differential expression of miR-372-5p using RT-qRCR in colorectal cancer and adjacent tissues, colorectal cancer cells and normal intestinal epithelial cells. Bioinformatic analysis and double luciferase assay were performed for verification of the targeting relationship between miR-372-5p and PTEN. Western blotting was used to assess the effects of transfection with miR-372-5p inhibitor and miR-372-5p mimics alone, co-transfection with miR-372-5p inhibitor and si-PTEN, and co-transfection with miR-372-5p mimics and PI3K inhibitor on the expressions of PTEN and CXCL12 and the activation of PI3K/AKT signal pathway; Transwell assay and scratch assay were used to examine the changes in the migration ability of the transfected cells, the cells co-transfected with miR-372-5p mimics and si-CXCL12, and the cells treated with conditioned medium from HCT116 cells transfected with miR-372-5p mimics. RESULTS: The expression of miR-372-5p was significantly higher in colorectal cancer tissues than in adjacent tissues, and higher in HCT116 and SW620 cells than in NCM460 cells (P < 0.01). Double luciferase assay confirmed that PTEN was a potential target gene of miR-372-5p (P < 0.05). Transfection of HCT116 cells with miR-372-5p mimics obviously decreased PTEN protein expression, increase CXCL12 expression and the phosphorylation level of AKT, and lowered the cell migration ability, while transfection with miR-372-5p inhibitor produced the opposite effects (P < 0.05); si-PTEN obviously neutralized the effect of miR-372-5p inhibitor (P < 0.01). PI3K inhibitor significantly decreased CXCL12 expression and inhibited the cell migration (P < 0.05), and this effect was mitigated by miR-372-5p mimics (P < 0.01). Treatment with the conditioned medium from HCT116 cells transfected with miR-372-5p mimics significantly enhanced the migration ability of NCM460 cells, and this effect was suppressed by transfection with si-CXCL12 (P < 0.01). CONCLUSION MiR-372-5p activates PI3K/AKT signaling pathway by targeting PTEN and up-regulates CXCL12 expression to promoting metastasis of colorectal cancer cells.
Chemokine CXCL12/metabolism* ; Colorectal Neoplasms/pathology* ; Culture Media, Conditioned ; Humans ; MicroRNAs/metabolism* ; Neoplasm Metastasis ; PTEN Phosphohydrolase/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Signal Transduction

CXCL12/CXCR4 axis composed of chemokine CXCL12 and its specific ligand CXCR4 can regulate and control the adhesion of leukemia cells to protective bone marrow niche, promote cell survival, and resist apoptosis induced by signal transduction inhibitors and chemotherapeutic drugs. Therefore, CXCL12 /CXCR4 axis has become a new target for the treatment of acute myeloid leukemia. At present, CXCR4 inhibitors that have been developed are in different clinical trials, showing good anti-leukemia effect. In this review, the research advance of CXCR4 inhibitors in the treatment of acute myeloid leukemia is summarized briefly.
Antineoplastic Agents/therapeutic use* ; Apoptosis ; Bone Marrow ; Chemokine CXCL12/pharmacology* ; Humans ; Leukemia, Myeloid, Acute/drug therapy* ; Receptors, CXCR4 ; Signal Transduction

BACKGROUND: There is growing evidence that 5-fluorouracil (5-FU) combined with therapeutic trauma can effectively induce skin repigmentation in vitiligo patients who are unresponsive to conventional treatments. Previous studies have mainly focused on identifying the antimitotic activity of 5-FU for the treatment of skin cancer, but few studies have investigated its extra-genotoxic actions favoring melanocyte recruitment. METHODS: We utilized the full thickness excisional skin wound model in Dct-LacZ transgenic mice to dynamically assess the migration of melanocytes in the margins of wounds treated with or without 5-FU. The in-situ expression of CXCL12 was examined in the wound beds using immunofluorescence staining. Quantitative real-time polymerase chain reaction and Western blotting analyses were performed to detect the expression levels of CXCL12 mRNA and protein in primary mouse dermal fibroblasts treated with or without 5-FU. Transwell assays and fluorescein isothiocyanate (FITC)-phalloidin staining were used to observe cell migration and filamentous actin (F-actin) changes of melan-a murine melanocytes. RESULTS: Whole mount and cryosection X-gal staining showed that the cell numbers of LacZ-positive melanocytes were much higher in the margins of dorsal and tail skin wounds treated with 5-FU compared with the controls. Meanwhile, CXCL12 immunostaining was significantly increased in the dermal compartment of wounds treated with 5-FU (control vs. 5-FU, 22.47 ± 8.85 vs. 44.69 ± 5.97, P < 0.05). Moreover, 5-FU significantly upregulated the expression levels of CXCL12 mRNA (control vs. 5-FU, 1.00 ± 0.08 vs. 1.54 ± 0.06, P < 0.05) and protein (control vs. 5-FU, 1.00 ± 0.06 vs. 2.93 ± 0.10, P < 0.05) in cultured fibroblasts. Inhibition of the CXCL12/CXCR4 axis suppressed melanocyte migration in vitro using a CXCL12 small interfering RNA (siRNA) or a CXCR4 antagonist (AMD3100). CONCLUSION 5-FU possesses a pro-pigmentary activity through activation of the CXCL12/CXCR4 axis to drive the chemotactic migration of melanocytes.
Animals ; Cell Movement ; Cell Proliferation ; Chemokine CXCL12/genetics* ; Fibroblasts ; Fluorouracil/therapeutic use* ; Humans ; Mice ; RNA, Messenger ; Receptors, CXCR4

OBJECTIVE: To investigate the role of IL-17A in promoting the activation of lung fibroblasts and the secretion of chemokine CXCL12, and to explore the possible mechanism. METHODS: Lung tissues of BALB/c mice were collected after intraperitoneal injection of recombinant mouse IL-17A (rmIL-17A). Real-time RT-PCR and Western blotting were used to detect the expression levels of α-smooth muscle actin (α-SMA) and collagen I in lung tissues, and immunohistochemical staining and real-time RT-PCR were used to determine the expression of CXCL12. Normal mouse primary lung fibroblasts were isolated and cultured, and identified by immunofluorescence staining with optical microscopy. Cells and supernatant of culture medium were collected after stimulation with rmIL-17A at different concentrations. mRNA levels of α-SMA, collagen I, and CXCL12 in the cells were determined by real-time RT-PCR, and the levels of collagen I and CXCL12 in the supernatant of culture medium were determined by ELISA. RESULTS: The mRNA and protein levels of α-SMA and collagen I in the lung tissue of mice injected with rmIL-17A were significantly increased compared with the control group (all CONCLUSIONS s: IL-17A can promote the activation of lung fibroblasts and translation into myofibroblast. The secretion of collagen is increased, which promote the deposition of extracullular matrix, and leads to the occurrence and development of lung fibrosis. CXCL12, a chemokine secreted by activated fibroblasts, may be involved in this process.
Actins/genetics* ; Animals ; Cells, Cultured ; Chemokine CXCL12/metabolism* ; Fibroblasts/metabolism* ; Interleukin-17/pharmacology* ; Lung/metabolism* ; Mice ; Mice, Inbred BALB C

OBJECTIVE: To investigate the expressions of stromal cell-derived factor (CXCL12), stromal cell-derived factor receptor (CXCR4), vascular endothelial growth factor (VEGF) and microvessel density (MVD) in bone marrow microsputum of patients with multiple myeloma (MM) and their correlation with the prognosis. METHODS: The expressions of CXCL12, CXCR4, VEGF and MVD in bone marrow microtubules of 57 newly diagnosed MM patients and 26 normal bone marrow samples were detected by immunohistochemistry. The rank sum test was used to compare the differences between the two groups. The clinical data of the patients were collected to analyze the correlation between the indicators of the MM group and the prognosis. RESULTS: The expressions of CXCL12, CXCR4, VEGF and MVD in the bone marrow biopsy of the patients in MM group were significantly higher than those in the normal control group (P＜0.05). The expressions levels of CXCL12, CXCR4, VEGF and MVD were in the bone marrow of the patients in MM group were correlated with the ISS stage, risk stratification and the proportion of plasma cells in the bone marrow (P＜0.05). Univariate analysis showed that age, ISS stage, risk stratification, plasma cell ratio, expressions of CXCL12, CXCR4, VEGF, and MVD associated with the prognosis of patients with MM (P＜0.05). Multivariate analysis found that expressions of CXCR4, VEGF, MVD, age, and plasma cell ratio were independent prognostic factors. CONCLUSION The expressions of CXCL12, CXCR4, VEGF and MVD are increase in the bone marrow of patients with multiple myeloma, and their expressions levels are associate with the occurrence and development of multiple myeloma, and their high expression may indicate a poor prognosis.
Chemokine CXCL12 ; Humans ; Multiple Myeloma ; Neovascularization, Pathologic ; Patients ; Prognosis ; Receptors, CXCR4 ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factors

OBJECTIVE: To investigate the effect of chronic emotional stimulation induced by empty bottle stimulation on CXCL12/CXCR4-mediated inflammatory response in rats with acute myocardial infarction (AMI). METHODS: Rat models of anxiety were established by a 21-day stimulation with uncertain empty bottle drinking water, and myocardial infarction was induced by ligating the left anterior descending branch of the coronary artery; compound models were established by performing myocardial infarction operation on the 15th day of anxiety modeling. The rats were randomly divided into 4 groups: shamoperated group (=6), myocardial infarction group (=6), compound model group (with myocardial infarcted and anxiety; = 6), and inhibitor group (compound models treated daily with 1 mg/kg AMD3100 for 6 days; =7). Echocardiography was used to examine the LVEF and LVFS to evaluate the cardiac function of the rats. Elevated maze test and open field test were used to evaluate the behaviors of the rats. The expressions of CXCL12, CXCR4, IL-1β, IL-18 and neutrophil active protease (NE) in the myocardial tissues and blood samples were detected with ELISA and immunohistochemistry. RESULTS: The LVEF and LVFS were lower in the compound model group than in the sham group and myocardial infarction group ( < 0.05), and were higher in inhibitor group than in the compound model group ( < 0.05). LVID; d and LVID; s were lower in the inhibitor group than in the compound model group ( < 0.05). Compared to those in the sham group and myocardial infarction group, the rats in the compound model group more obviously preferred to stay in the closed arm ( < 0.05) in EPM; the rats in the inhibitor group had more times of entering and staying in the open arm than the compound model rats ( < 0.05); the horizontal and vertical movements were less in the compound model rats than in those in the sham group and the myocardial infarction group ( < 0.05) in OFT, and the vertical movement of the rats in inhibitor group was higher than those in the compound model group ( < 0.05). The expression of CXCR4 in the marginal zone of myocardial infarction was significantly higher in the compound model group than in the sham-operated group, myocardial infarction group and inhibitor group ( < 0.05). The expressions of IL-1β, IL-18 and NE in the inhibitor group were significantly lower than those in the compound model group ( < 0.05). Compared with at in the sham-operated group, the number of Nissl bodies in the compound model group decreased significantly ( < 0.01). CONCLUSIONS Chronic emotional stress induced by empty bottle stimulation can lead to dysfunction of the CXCL12/CXCR4 axis, which causes inflammatory cascade after myocardial infarction to worsen myocardial cell necrosis, cardiac function and hippocampal neuronal damage after the infarction.
Animals ; Chemokine CXCL12 ; Coronary Vessels ; Emotions ; Myocardial Infarction ; Myocardium ; Psychological Distress ; Rats ; Receptors, CXCR4 ; Signal Transduction