Aerobic exercise modulates the TGF-β1/Smad/miR-21 molecular pathway to improve the mechanism of hepatic fibrosis in aging mice
10.3969/j.issn.1001-1242.2025.10.003
- VernacularTitle:有氧运动调控TGF-β1/Smad/miR-21分子通路改善衰老小鼠肝纤维化的机制研究
- Author:
Bao'ai WU
1
;
Zhibin ZHANG
1
;
Chuanqi JU
1
Author Information
1. 山西大学体育学院,山西省 太原市,030006
- Publication Type:Journal Article
- Keywords:
aerobic exercise;
liver fibrosis;
transforming growth factor-β;
miRNA-21;
SMAD family member 7
- From:
Chinese Journal of Rehabilitation Medicine
2025;40(10):1466-1473,1518
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the effect and underlaying mechanism of aerobic exercise on aging-induced hepatic fi-brosis.Method:Thirty-two SPF grade C57BL/6J male mice were used,including 16 mice aged 2 months(young group)and 16 mice aged 19 months(senescent group).Both the aging group and the young group underwent one week of acclimatization.The animals were randomly divided into four groups:young control group(Y group),young exercise group(YE group),aging control group(A group)and aging exercise group(AE group),with 8 animals in each group.The experiment carried out exercise intervention in the way of running on the treadmill.All the exercise mice in each group received adaptive exercise with increasing load for one week,and then received formal aerobic exercise intervention for 12 weeks according to the protocol.HE,Mas-son and Sirius scarlet staining were used to observe the pathological morphology of liver tissue.The levels of Collagen Ⅰ and α-SMA in liver were observed by immunohistochemical staining.The mRNA expressions of miR-21,Collagen Ⅰ,α-smooth muscle actin(α-SMA),transforming growth factor-β1(TGF-β1)and SMAD7 in liver tissues were detected by q-PCR.Western Blot assay was used to detect the protein expressions of Collagen Ⅰ,α-SMA,CTGF,TGF-β1,TGF-β receptor Ⅱ(TβR-Ⅱ),Smad7 and P-Smad2/3 in liver tissues.Result:Compared with Y group,hepatocyte degeneration and fiber deposition were observed in group A.The mRNA and protein levels of Collagen Ⅰ,α-SMA,CTGF,TGF-β1,TβR-Ⅱ,P-SMAD2/3 and miR-21 in liver tissues were significantly increased(P<0.05),while the level of Smad7 was significantly decreased(P<0.05).After exercise intervention,liver tissue degeneration and fiber deposition were alleviated in the AE group,and the expressions of Collagen Ⅰ,α-SMA,CTGF,TGF-β1,TβR-Ⅱ,P-Smad2/3 and miR-21 in liver tissue were significantly decreased(P<0.05),the level of Smad7 was significantly increased(P<0.05).Conclusion:Aerobic exercise can effectively improve age-induced hepatic fibrosis.The underlying mechanism may be related to inhibiting the overexpression of TGF-β1,reducing the expression of TGF-β1/Smad signaling pathway related molecules,inhibiting miR-21,improving the activity of Smad7,and reducing the deposition of liver cell fibers.
