TGF-β/Smad and JAK/STAT pathways are involved in the anti-fibrotic effects of propylene glycol alginate sodium sulphate on hepatic fibrosis.
Shizan XuYuqing MaoJianye WuJiao FengJingjing LiLiwei WuQiang YuYuting ZhouJie ZhangJiaojiao ChenJie JiKan ChenFan WangWeiqi DaiXiaoming FanChuan-Yong GuoPublished in: Journal of cellular and molecular medicine (2020)
Liver fibrosis, a consequence of unhealthy modern lifestyles, has a growing impact on human health, particularly in developed countries. Here, we have explored the anti-fibrotic effects of propylene glycol alginate sodium sulphate (PSS), a natural extract from brown algae, in fibrotic mice and cell models. Thus, we established bile duct ligature and carbon tetrachloride mouse models and LX-2 cell models with or without PSS treatment. Liver pathological sections and the relevant indicators in serum and liver tissues were examined. PSS prevented hepatic injury and fibrosis to a significant extent, and induced up-regulation of matrix metalloproteinase-2 and down-regulation of tissue inhibitor of metalloproteinase-1 through suppressing the transforming growth factor β1 (TGF-β1)/Smad pathway. PSS additionally exerted an anti-autophagy effect through suppressing the Janus kinase (JAK) 2/transducer and activator of transcription 3 (STAT3) pathway. In conclusion, PSS prevents hepatic fibrosis by suppressing inflammation, promoting extracellular matrix (ECM) decomposition and inactivating hepatic stellate cells through mechanisms involving the TGF-β1/Smad2/3 and JAK2/STAT3 pathways in vivo and in vitro.
Keyphrases
- transforming growth factor
- liver fibrosis
- epithelial mesenchymal transition
- extracellular matrix
- human health
- signaling pathway
- oxidative stress
- induced apoptosis
- systemic sclerosis
- risk assessment
- single cell
- idiopathic pulmonary fibrosis
- mouse model
- cell therapy
- endoplasmic reticulum stress
- cell death
- diabetic rats
- cell proliferation
- climate change
- type diabetes
- transcription factor
- cell cycle arrest
- adipose tissue
- immune response
- metabolic syndrome
- wound healing
- bone marrow
- nuclear factor
- replacement therapy
- toll like receptor