Transforming growth factor-β signaling: From tissue fibrosis to therapeutic opportunities

Ren, Lili; Li, Xiaojun; Duan, Tingting; Li, Zheng-Hai; Yang, Junzheng; Zhang, Yamei; Zou, Liang; Miao, Hua; Zhao, Ying-Yong

doi:10.1016/j.cbi.2022.110289

Cited by 64 publications

(38 citation statements)

References 132 publications

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“…Chronic kidney injury and inflammation lead to the final end point of renal fibrosis . In addition, a wide array of evidence have demonstrated that UA could directly undergo renal fibrosis. ,, Pathophysiological renal fibrosis is essentially an exaggerated deposition of the ECM commonly found in the glomerulus and interstitial area, resulting in the loss of normal nephrons and a progressive decline in function. , ECM in interstitial fibrosis is predominantly composed of collagen (I, III, IV, and V) and also contains fibronectin, laminin, and heparan. In the glomerulus, ECM was produced and deposited in mesangial cells and obstructed glomerular capillaries, thus causing a focal segmental glomerulosclerosis (FSGS) .…”

Section: Discussionmentioning

confidence: 99%

Fucoidan from Saccharina japonica Alleviates Hyperuricemia-Induced Renal Fibrosis through Inhibiting the JAK2/STAT3 Signaling Pathway

Sun

Liu

Zhang

et al. 2023

J. Agric. Food Chem.

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Fucoidan is a native sulfated polysaccharide mainly isolated from brown seaweed, with diverse pharmacological activities, such as anti-inflammatory and antifibrosis. Hyperuricemia (HUA) is a common metabolic disease worldwide and mainly causes hyperuricemic nephropathy, including chronic kidney disease and end-stage renal fibrosis. The present study investigated the protective function of fucoidan in renal fibrosis and its pharmacological mechanism. The renal fibrotic model was established with the administration of potassium oxonate for 10 weeks. The protein levels of related factors were assessed in HUA mice by an enzyme-linked immunosorbent assay (ELISA) and western blotting. The results showed that fucoidan significantly reduced the levels of serum uric acid, blood urea nitrogen (BUN), α-smooth muscle actin (α-SMA), and collagen I, and improved kidney pathological changes. Furthermore, renal fibrosis had been remarkably elevated through the inhibition of the epithelial-to-mesenchymal transition (EMT) progression after fucoidan intervention, suppressing the Janus kinase 2 (JAK2) signal transducer and activator of transcription protein 3 (STAT3) signaling pathway activation. Together, this study provides experimental evidence that fucoidan may protect against hyperuricemia-induced renal fibrosis via downregulation of the JAK2/STAT3 signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Fucoidan from Saccharina japonica Alleviates Hyperuricemia-Induced Renal Fibrosis through Inhibiting the JAK2/STAT3 Signaling Pathway

Sun

Liu

Zhang

et al. 2023

J. Agric. Food Chem.

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“…japonicum -infected mice [ 75 ]. TGF-β is secreted by a variety of immune cells through the Smad pathway; further promoting the elevated levels of TIMP1, α-SMA, and collagen 1/2 during the HSC to myofibroblast transition, formatting and remodeling the ECM, and eventually leading to liver fibrosis [ 76 ]. Our data also showed that TGF-β secreted by PBMC with the SEA treatment causes activation of the LX-2 cells and leads to the upregulation of hepatic fibrotic markers α-SMA and collagen 1.…”

Section: Discussionmentioning

confidence: 99%

Differential Analysis of Key Proteins Related to Fibrosis and Inflammation in Soluble Egg Antigen of Schistosoma mansoni at Different Infection Times

Chen

Peng

et al. 2023

Pathogens

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Schistosomiasis is a major global health problem. Schistosomes secrete antigens into the host tissue that bind to chemokines or inhibit immune cell receptors, regulating the immune responses to allow schistosome development. However, the detailed mechanism of chronic schistosome infection-induced liver fibrosis, including the relationship between secreted soluble egg antigen (SEA) and hepatic stellate cell (HSC) activation, is still unknown. We used mass spectrometry to identify the SEA protein sequences from different infection weeks. In the 10th and 12th infection weeks, we focused on the SEA components and screened out the special protein components, particularly fibrosis- and inflammation-related protein sequences. Our results have identified heat shock proteins, phosphorylation-associated enzymes, or kinases, such as Sm16, GSTA3, GPCRs, EF1-α, MMP7, and other proteins linked to schistosome-induced liver fibrosis. After sorting, we found many special proteins related to fibrosis and inflammation, but studies proving their association with schistosomiasis infection are limited. Follow-up studies on MICOS, MATE1, 14-3-3 epsilon, and CDCP1 are needed. We treated the LX-2 cells with the SEA from the 8th, 10th, and 12th infection weeks to test HSC activation. In a trans-well cell model in which PBMCs and HSCs were co-cultured, the SEA could significantly induce TGF-β secretion, especially from the 12th week of infection. Our data also showed that TGF-β secreted by PBMC after the SEA treatment activates LX-2 and upregulates hepatic fibrotic markers α-SMA and collagen 1. Based on these results, the CUB domain-containing protein 1 (CDCP1) screened at the 12th infection week could be investigated further. This study clarifies the trend of immune mechanism variation in the different stages of schistosome infection. However, how egg-induced immune response transformation causes liver tissue fibrosis needs to be studied further.

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“…TGF-β is the most potent cytokine that promotes fibrosis by contributing to the activation of hepatic stellate cells, and hepatic stellate cells themselves are the primary source of TGF-β production. PDGF is the most potent cytokine that promotes the division and proliferation of hepatic stellate cells [22].…”

Section: Discussionmentioning

confidence: 99%

Inhibition of liver fibrosis by sensitization of human hepatic stellate cells by combined treatment with galtanin and TARIL

Moon

2023

JABC

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Liver fibrosis is caused by metabolic problems such as cholestasis, genetic problems, or viral infections. Inhibiting hepatic stellate cell (HSC) activation or inducing selective apoptosis of activated HSCs is used as a treatment strategy for liver fibrosis. It has been reported that when HSCs are activated, their apoptosis sensitivity to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is enhanced because the expression of death receptor 5 is elevated. Finding a natural compound that can enhance the apoptotic effect of TRAIL on HSCs is a necessary strategy for liver fibrosis treatment. It was confirmed here that mangosteenderived gartanin increased the effect of TRAIL-induced apoptosis by increasing the expression of DR5 in a p38-dependent manner in the hepatic stellate cell line LX-2. Combined treatment with gartanin and TRAIL accelerated DNA cleavage through caspase-3 activation and enhanced antifibrotic effects in LX-2 cells.

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Transforming growth factor-β signaling: From tissue fibrosis to therapeutic opportunities

Cited by 64 publications

References 132 publications

Fucoidan from Saccharina japonica Alleviates Hyperuricemia-Induced Renal Fibrosis through Inhibiting the JAK2/STAT3 Signaling Pathway

Fucoidan from Saccharina japonica Alleviates Hyperuricemia-Induced Renal Fibrosis through Inhibiting the JAK2/STAT3 Signaling Pathway

Differential Analysis of Key Proteins Related to Fibrosis and Inflammation in Soluble Egg Antigen of Schistosoma mansoni at Different Infection Times

Inhibition of liver fibrosis by sensitization of human hepatic stellate cells by combined treatment with galtanin and TARIL

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