scholarly journals Expressions of TOLL-like receptor 4 (TLR-4) and matrix metalloproteinase 9 (MMP-9)/Tissue inhibitor of metalloproteinase 1 (TIMP-1) in pulmonary blood vessels with chronic obstructive pulmonary diseases and their relationships with pulmonary vascular remodelling

2018 ◽  
Vol 64 (4) ◽  
pp. 361-367 ◽  
Author(s):  
Wen-Cheng Yu ◽  
Jin-Peng Cong ◽  
Li-Yun Mi

SUMMARY OBJECTIVE: This study aims at investigating the expressions of TOLL-like receptor 4 (TLR-4) and matrix metalloproteinase 9 (MMP-9)/ tissue inhibitor of metalloproteinase 1 (TIMP-1) in pulmonary blood vessels with chronic obstructive pulmonary disease (COPD) and their relationships with pulmonary vascular remodelling (PVR). METHODS: 60 para-tumour tissues were divided into the COPD group and the control group (n=30); the inflammations, pulmonary artery wall area/total artery area (WA%), and wall thickness/vascular outer diameter (WT%) were compared. The expressions of TLR-4, MMP-9/TIMP-1, and PCNA in pulmonary vascular smooth muscle cells were detected, and their relationships with PVR were then analysed. RESULTS: The inflammations (1.6±0.8), WA% (44.0±6.4), and WT% (27.3±3.3) in the COPD group were higher than in the control group (0.3±0.5, 26.1±2.8, 15.6±1.8), and the expressions of TLR-4 (31.4±147) and MMP-9/TIMP-1 (2.2±2.6) were increased compared to the control group (4.7±4.5, 1.9±12). Correlation analysis: TLR-4 and MMP-9/TIMP-1 were positively correlated with the inflammations (r=0.18, P<0.01), WA% (r=0.68, P<0.01), and WT% (r=0.73, P<0.01), as well as positively correlated with the expression of PCNA (r=0.44, P<0.01); the upregulation of TLR-4 was positively correlated with the expressions of MMP-9 and TIMP-1. CONCLUSIONS: The upregulation of TLR-4 in the pulmonary arterial smooth muscle cells of COPD patients could promote the inflammations and the MMP-9 expression, thus causing abnormal degradation of extracellular matrix, so it played an important role in the process of PVR.

2009 ◽  
Vol 99 (6) ◽  
pp. 489-496 ◽  
Author(s):  
Chuan Yang ◽  
Ping Zhu ◽  
Li Yan ◽  
Lihong Chen ◽  
Ren Meng ◽  
...  

Background: We investigated the mechanism of delayed would healing caused by diabetes and measured the dynamic changes in matrix metalloproteinase 9 (MMP-9) and tissue inhibitor of metalloproteinase 1 (TIMP-1) levels. We noted differences in the ratio of MMP-9 to TIMP-1 in the wounds of diabetic and nondiabetic rats.Methods: Forty-two Sprague-Dawley rats weighing 250 g were randomly assigned to either the control group or the streptozotocin-induced diabetes group. Then, full-thickness excision wounds were created on the middle of the back of each animal. Skin biopsy specimens were obtained on days 0, 3, 7, and 14 after incision. The content of collagen was quantified by Masson’s staining and the macrophage marker, and CD68 was detected by immunohistochemical analysis. Messenger RNA and protein expression of MMP-9 and TIMP-1 was measured by reverse transcriptase–polymerase chain reaction and Western blot, respectively.Results: Diabetic rats exhibited slower wound healing than control animals (P &lt; .05). On days 3, 7, and 14 after incision, higher levels of MMP-9 messenger RNA and protein expression were detected in the diabetic group compared with the control group (P &lt; .05), and expression of TIMP-1 messenger RNA and protein was significantly decreased. In addition, the ratio of MMP-9 to TIMP-1 was stable in controls, whereas there was a marked increase in the ratio in diabetic skin wounds.Conclusions: The balance between MMP-9 and its inhibitor, TIMP-1, is disturbed in diabetic skin tissue after injury, which may lead to histologic abnormality of diabetic skin and delayed wound healing. (J Am Podiatr Med Assoc 99(6): 489–496, 2009)


Biomolecules ◽  
2019 ◽  
Vol 9 (2) ◽  
pp. 62 ◽  
Author(s):  
Pelin Uysal ◽  
Hafize Uzun

Chronic obstructive pulmonary disease (COPD) is influenced by genetic and environmental factors. A protease-antiprotease imbalance has been suggested as a possible pathogenic mechanism for COPD. Here, we examined the relationship between circulating serpina3g, matrix metalloproteinase-9 (MMP-9), and tissue inhibitor of metalloproteinase-1 and -2 (TIMP-1 and -2, respectively) and severity of COPD. We included 150 stable COPD patients and 35 control subjects in the study. The COPD patients were classified into four groups (I, II, III, and IV), according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines based on the severity of symptoms and the exacerbation risk. Plasma serpina3g, MMP-9, and TIMP-1 and -2 concentrations were significantly higher in the all patients than in control subjects. Plasma serpina3g, MMP-9, and TIMP-1 and -2 concentrations were significantly higher in groups III and IV than in groups I and II. A negative correlation between serpina3g, MMP-9, and TIMP-1 and -2 levels and the forced expiratory volume in 1 s (FEV1) was observed. MMP-9 concentration and the MMP-9/TIMP-1 ratio were higher in patients with emphysema than in other phenotypes (both with p < 0.01). The findings of this study suggest that circulating serpina3g, MMP-9, and TIMP-1 and -2 levels may play an important role in airway remodeling in COPD pathogenesis. Disrupted protease-antiprotease imbalance in patients with COPD is related to the presence of airway injury. MMP-9 concentration and the MMP-9/TIMP-1 ratio are the best predictors of emphysema in COPD patients.


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