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Axonal demyelination is an important factor causing neurological dysfunction after spinal cord injury. Retaining the integrity of myelin sheath and promoting remyelination play an important role in the functional recovery of spinal cord injury. The bottleneck of the failure of remyelination is the inability of myelin-forming cells (oligodendrocytes and Schwann cells) to differentiate and mature. In recent years related research on spinal cord injury demyelination has found that cell transplantation, neuregulin-1 and hydrogel can effectively enhance remyelination, and identified aquaporin-4 (aquaporin-4, AQP4), metal-loproteinase (Matrix metailoproteinase, MMP) may be a potential therapeutic target to promote myelin recovery after spinal cord injury. This review discusses the research progress of enhancing remyelination after spinal cord injury, providing ideas for the further development of new methods for the treatment of spinal cord injury.
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Objective:To explore the efficacy and mechanism of Qingfei Huatan Tang on chronic obstructive pulmonary disease (COPD). Method:The rat model of COPD was established through smoke inhalation combined with lipopolysaccharide (LPS) and pulmonary compound injection. After successful modeling, the rats were randomly divided into 6 groups, namely the control group, the COPD model group, low, medium and high-dose Qingfei Huatan Tang groups and the ambroxol group. After 28 days of modeling, the drug was administered. Low, medium and high-dose Qingfei Huatan Tang (7.5, 15, 30 g·kg-1) and ambroxol (35 mg·kg-1) were administered continuously for 14 days. Immunohistochemistry and Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) were used to detect protein expression and mRNA expression of cystic fibrosis transmembrane conductance regulator (CFTR) in pulmonary fibrosis. NCI-H292 cells were induced by LPS to establish a mucus hypersecretion model. The experiment was divided into 8 groups, namely the blank control group, LPS group, LPS+10% fetal bovine serum group, LPS+ physiological serum group, LPS+5% drug serum group, LPS+10% drug serum group, LPS+20% drug serum group and LPS+AG490 group. Immunofluorescence, Western blot and Real-time PCR were used to observe the protein and mRNA expressions of CFTR in NCI-H292 cells after LPS stimulation, and western blot was used to detect the expression of tyrosine kinase 2/transcription factor 3 (JAK2/STAT3) signaling pathway in NCI-H292 cells after LPS stimulation. Result:There were a large number of brown particles around the lumen of lung tissues in the normal group, with increased COPD expression. There were a few brown particles around the lumen of lung tissues in the model group compared with the normal group, with decreased COPD expression. Compared with the normal group, mRNA and protein expressions of CFTR in the lung tissues of the COPD model group were significantly decreased (P<0.05). Compared with the model group, mRNA and protein expressions of CFTR in the lung tissues of low, medium and high-dose Qingfei Huatan Tang groups (P<0.05). Compared with the blank control group, mRNA and protein expressions of CFTR in NCI-H292 cells of the LPS group (P<0.05), with significant increases in protein expressions of p-JAK2 and p-STAT3 (P<0.05). Compared with the model group, 5%, 10%, 20% Qingfei Huatan Tang-containing serum groups showed significant increases in mRNA and protein expressions of CFTR, but with significant decreases in p-JAK2, p-STAT3 protein expressions (P<0.05, P<0.01). Conclusion:Qingfei Huatan Tang up-regulated CFTR in the treatment of COPD by inhibiting JAK2/STAT3 pathway.
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OBJECTIVE@#To examine the expression of matrix metalloproteinase-9 (MMP-9) in human bronchial epithelial cells treated with calcitonin-gene-related peptide (CGRP).@*METHODS@#RT-PCR and gelatin zymography were performed to examine the dynamic expression and activity of MMP-9 in human bronchial epithelial cells at different doses (10(-10), 10(-9), 10(-8), 10(-7), and 10(-6)mol/L) and different time points (6,12,18,24,36, and 48h) after the stimulation of CGRP.@*RESULTS@#The unstimulated human bronchial epithelial cells only secreted a small amount of MMP-9. After the CGRP stimulation, the expression of MMP-9 presented in a concentration-dependent (10(-10), 10(-9), 10(-8), 10(-7), and 10(-6) mol/L) and time-dependent (6,12,18,24,36, and 48 h) manners (P<0.01) in human bronchial epithelial cells. The effect of CGRP could be diminished by H-7 and W-7, an antagonist of protein kinase C (PKC) and calmodulin (CaM) (P<0.05).@*CONCLUSION@#CGRP can stimulate the secretion and expression of MMP-9 in human bronchial epithelial cells, and the signal transduction is partly via the PKC and CaM pathway.
Subject(s)
Humans , Bronchi , Cell Biology , Calcitonin Gene-Related Peptide , Pharmacology , Calmodulin , Metabolism , Cells, Cultured , Epithelial Cells , Metabolism , Matrix Metalloproteinase 9 , Metabolism , Protein Kinase C , Metabolism , Signal TransductionABSTRACT
<p><b>AIM</b>To explore the effects of calcitonin-gene-related peptide (CGRP) on LPS-induced MMP-9 secretion by alveolar macrophages (AM) in vitro.</p><p><b>METHODS</b>The supernatant of LPS-induced Wistar rat AM from different intervention groups were collected to measure the activity by gelatin zymography.</p><p><b>RESULTS</b>(Only secreting a small amount of MMP-9 with unstimulated AM, LPS stimulated MMP-9 production in a concentration-dependent manner (p < 0.01). (2) The activity of MMP-9 in CGRP intervention groups at different levels were significantly lower than those in non-intervention group (p < 0.01). (3) The inhibiting effects of CGRP were diminished by H-7 and W-7, an antagonist of protein kinase C (PKC) and calmodulin (CaM) (p < 0.05).</p><p><b>CONCLUSION</b>These data suggested that CGRP involved in the MMP-9 secretion by AM, partly, via PKC and CaM pathway.</p>