Effects of 6-weeks of continuous and HIIT training on gene expression of TGF-B, MMP-2 and TIMP-1 in lung tissues of male wistar rats

In pathological studies, there is usually a low degree of Pulmonary inflammation, and due to the presence of inflammatory cells in the lung tissue, there are discussions about the role of these cells in the progression of the disease (1). Matrix metalloproteinases (MMPs) are super family of proteolytic enzymes that play an important role in the breakdown of extracellular matrix and fibrosis (2, 3). MMP-2 has the potential to degrade wide range of extracellular matrix proteins, including type IV collagen, basement membrane, fibronectin and gelatin (6). Studies show that MMP-2 activity is increased in pulmonary fibrosis (7).The Tissue Inhibitor of MMPs (TIMPs) gene family are physiological inhibitors of MMPs that inhibit the activity of these proteases. TIMP / MMP imbalance is an important factor in the fibrogenic process (9). Also, in pulmonary fibrosis, the activity of MMPs is regulated by several factors, including growth factor, and inflammatory mediators may play an important role in modulating lung tissue damage and extracellular matrix degradation. Transforming Growth Factor β (TGF-β) is a multifunctional cytokine that plays an important role in causing fibrosis in many tissues, including the lungs (10).Studies show that exercise can help improve the levels of matrix metalloproteinases and their associated inflammatory factors. However, the results of studies in this field are contradictory, so, decrease in expression and serum levels of MMP-2 in rats following voluntary exercise and High-intensity interval training (HIIT) have been reported (12,13). On the other hand, 12 weeks of resistance training has been shown to increase MMP2 levels in rats (14). Also, significant increase (15) and no change (16) in TGF-β1 tissue values after HIIT was reported in rats.The effect of different training methods on lung tissue has been considered. Therefore, the aim of this study was to investigate the effects of 6-weeks of continuous and HIIT training on gene expression of TGF-B, MMP-2 and TIMP-1 in lung tissues of male wistar rats.

This is a experimental study. 18 male wistar rats (6 to 8 months) were selected and randomly divided into three groups of control (Con), moderate intensity continuous training (MICT) and High-intensity interval training (HIIT) groups. The aerobic training program consisted of 15 to 30 minutes of treadmill running at 65-70% VO2max intensity, 5 days a week for 6 weeks. The HIIT program consisted of 5 to 8 alternations (2 minutes) of 80 to 100 percent VO2max and 2 minutes of recovery with 50 to 60 percent of VO2max between each period for 6 weeks (17). TGF-β, MMP-2 and TIMP-1 gene expression in lung tissue was measured after training using Real Time PCR. Data were analyzed by one-way ANOVA and LSD post hoc test at the P <0.05.

Table 4 shows the mean and standard deviation of research variables in different groups. The results showed that HIIT and MICT led to significant decrease in MMP-2 gene expression and significant increase in TIMP-1 and TGF-β gene expression in lung tissue compared to the control group (P=0.001). There was no significant difference in the relative expression of MMP-2 between the two groups of HIIT and MICT (P=0.832), but TIMP-1 and TGF-β gene expression was significantly higher in the HIIT group compared to the MICT group (P=0.001) (Fig. 1-3).

The findings of the present study show that HIIT and MICT significantly decrease MMP-2 gene expression and significantly increase TIMP-1 and TGF-β gene expression in lung tissues of male wistar rats. The findings of this study were consistent with the results of Previous research (12,13, 23, 27-29). Decreased gene expression of MMP-2 in response to training sessions can be attributed to the expression of endogenous protein inhibitors such as TIMP-1, alpha-2 macroglobulin and protease degradation. Also, the reduction of some inflammatory factors that stimulate MMP-2 due to interval training periods can play a role in this reduction (19). Therefore, according to the mechanisms involved in reducing MMP-2 expression and the findings of the present study, reducing MMP-2 in the HIIT and MICT groups compared to the control group can reduce the expression of TIMP-1 and TGF-β genes after exercise. MMPs are highly regulated at the level of gene transcription and translation in the lung, their expression is through a variety of transcription factors (activators and suppressors, including growth factors, hormones, cytokines, cell adhesion molecules, proteins), extracellular matrix and their bioactive components and intracellular signaling agents (GTPases), all of which can directly or indirectly regulate the expression of MMPs (20). Therefore, HIIT and MICT may alter the gene expression levels of the MMP-2 in lung tissue by affecting the above factors. The reason for the increase in TGF-β1 following exercise is not well understood. However, oxidative stress and exercise-induced hypoxia are two possible mechanisms (33). Studies have shown that by increasing the expression of NADPH oxidase and decreasing the expression of antioxidant enzymes, increases the expression of TGF-β1 in tissue (34,35). HITT is associated with hypoxia at the cell, which leads to increased expression of HIF-1α (Hypoxia-induced Factor 1- α). This factor increases in cells in response to hypoxia and mediates several biological functions. There were some limitations in the present study, such as the lack of measurement of other MMPs. According to the results, it seems that HIIT training may be a more effective intervention to reduce lung fibrosis. Therefore, it is recommended to consider High-intensity interval training programs for the health of the respiratory system.