Transplantation of adipose-derived stem cells ameliorates Echinococcus multilocularis-induced liver fibrosis in mice

Yang, Ning; Ma, Wenmei; Ke, Ying; Liu, Hui; Chu, Jin; Sun, Li; Lü, Guodong; Bi, Xiaojuan; Lin, Renyong

doi:10.1371/journal.pntd.0010175

Cited by 15 publications

(11 citation statements)

References 46 publications

(53 reference statements)

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“…2 D). This is consistent with studies in other organs, where increased TGF-β receptor expression was observed in damaged liver tissue, and its suppression reduced liver damage in mice 39 . Furthermore, TGF-β signaling increases its receptor expression on the cell surface, as well as enhances its own signaling responses, indicating the complex biological interactions between TGF-β and TGF-β receptors.…”

Section: Discussionsupporting

confidence: 92%

Suppression of the TGF-β signaling exacerbates degeneration of auditory neurons in kanamycin-induced ototoxicity in mice

Nitta,

Kurioka,

Mogi

et al. 2024

Sci Rep

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Transforming growth factor-β (TGF-β) signaling plays a significant role in multiple biological processes, including inflammation, immunity, and cell death. However, its specific impact on the cochlea remains unclear. In this study, we aimed to investigate the effects of TGF-β signaling suppression on auditory function and cochlear pathology in mice with kanamycin-induced ototoxicity. Kanamycin and furosemide (KM-FS) were systemically administered to 8-week-old C57/BL6 mice, followed by immediate topical application of a TGF-β receptor inhibitor (TGF-βRI) onto the round window membrane. Results showed significant TGF-β receptor upregulation in spiral ganglion neurons (SGNs) after KM-FA ototoxicity, whereas expression levels in the TGF-βRI treated group remained unchanged. Interestingly, despite no significant change in cochlear TGF-β expression after KM-FS ototoxicity, TGF-βRI treatment resulted in a significant decrease in TGF-β signaling. Regarding auditory function, TGF-βRI treatment offered no therapeutic effects on hearing thresholds and hair cell survival following KM-FS ototoxicity. However, SGN loss and macrophage infiltration were significantly increased with TGF-βRI treatment. These results imply that inhibition of TGF-β signaling after KM-FS ototoxicity promotes cochlear inflammation and SGN degeneration.

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Section: Discussionsupporting

confidence: 92%

Suppression of the TGF-β signaling exacerbates degeneration of auditory neurons in kanamycin-induced ototoxicity in mice

Nitta,

Kurioka,

Mogi

et al. 2024

Sci Rep

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“…Genome study indicated that E. multilocularis possesses TGF-β1, MAPK and Akt signaling pathways (Tsai et al, 2013;Zheng et al, 2013), beyond that, strong evidence suggest that during echinococccosis, the impaired host immune response is paralleled by an increased expression of TGF-β1 signaling components in periparasitic host cells and tissues (Nono et al, 2020). A later study on AE transplant treatment showed that through modulating the activity level of the TGF-β/Smad7 signaling pathway, liver fibrosis induced by E. multilocularis infection can be alleviated (Yang et al, 2022). In the present study, we observed apoptotic bodies in E. multilocularis PSC after treatment with PAB in vitro, referring apoptosis might be triggered.…”

Section: Groupsupporting

confidence: 56%

Suppressive effect of pseudolaric acid B on Echinococcus multilocularis involving regulation of TGF-β1 signaling in vitro and in vivo

Gao

Huo

et al. 2022

Front. Microbiol.

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Echinococcus multilocularis, the causative agent of alveolar echinococcosis (AE), severely threats human health and livestock farming. The first line of chemotherapeutic drug for AE is albendazole, which limits rapid extension of E. multilocularis metacestodes, but is rarely curative for AE, with severe side effects in long-term use, thus development of new anti-echinococcal drugs is mandated. Pseudolaric acid B (PAB) has long been used to treat fungal-infected dermatosis, and exerted anti-tumor, -fertility, -angiogenesis, -tubulin and antiparasitic activity. However, the effect of PAB against Echinococcus spp. remains unclear. The present study is to understand the effect of PAB against E. multilocularis in vitro and in vivo, and identify potential anti-echinococcal mechanism, as well as its toxicity. After exposure to PAB at 20 μg/ml, significant reduction of the survival rate and substantial ultrastructural destructions in E. multilocularis protoscoleces were observed in vitro. Furthermore, the wet weight of E. multilocularis cysts in the infected mice was significantly decreased after treatment with PAB (40, 20 or 10 mg/kg) for 12 weeks. Meanwhile, significant increase of both protein and mRNA expression of transforming growth factor beta 1 (TGF-β1) was detected in the serum and liver of the infected mice, whereas PAB administration lowered its expression significantly. The toxicity tests demonstrated that PAB displayed lower cytotoxicity to human liver and kidney cells (HL-7702 and HK-2 cell) with IC50 = 25.29 and 42.94 μg/ml than albendazole with IC50 = 3.71 and 21.22 μg/ml in vitro, and caused lower hepatoxicity and nephrotoxicity in mice than ABZ. Our findings indicated that PAB possesses potent anti-echinococcal effect, with lower toxicity than albendazole, implying a potential chemotherapeutic agent for AE. Additionally, the present study demonstrated that the suppressive effect of PAB on the parasite may involve down-regulation of TGF-β1 signaling.

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“… 545 ADSCs alleviated liver fibrosis in NASH mice by suppressing IL-17-mediated inflammation. 546 , 547 …”

Section: Novel Signaling Pathways and Pharmacological Targetsmentioning

confidence: 99%

Targeted therapeutics and novel signaling pathways in non-alcohol-associated fatty liver/steatohepatitis (NAFL/NASH)

Poulsen

et al. 2022

Sig Transduct Target Ther

128

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Non-alcohol-associated fatty liver/steatohepatitis (NAFL/NASH) has become the leading cause of liver disease worldwide. NASH, an advanced form of NAFL, can be progressive and more susceptible to developing cirrhosis and hepatocellular carcinoma. Currently, lifestyle interventions are the most essential and effective strategies for preventing and controlling NAFL without the development of fibrosis. While there are still limited appropriate drugs specifically to treat NAFL/NASH, growing progress is being seen in elucidating the pathogenesis and identifying therapeutic targets. In this review, we discussed recent developments in etiology and prospective therapeutic targets, as well as pharmacological candidates in pre/clinical trials and patents, with a focus on diabetes, hepatic lipid metabolism, inflammation, and fibrosis. Importantly, growing evidence elucidates that the disruption of the gut–liver axis and microbe-derived metabolites drive the pathogenesis of NAFL/NASH. Extracellular vesicles (EVs) act as a signaling mediator, resulting in lipid accumulation, macrophage and hepatic stellate cell activation, further promoting inflammation and liver fibrosis progression during the development of NAFL/NASH. Targeting gut microbiota or EVs may serve as new strategies for the treatment of NAFL/NASH. Finally, other mechanisms, such as cell therapy and genetic approaches, also have enormous therapeutic potential. Incorporating drugs with different mechanisms and personalized medicine may improve the efficacy to better benefit patients with NAFL/NASH.

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Transplantation of adipose-derived stem cells ameliorates Echinococcus multilocularis-induced liver fibrosis in mice

Cited by 15 publications

References 46 publications

Suppression of the TGF-β signaling exacerbates degeneration of auditory neurons in kanamycin-induced ototoxicity in mice

Suppression of the TGF-β signaling exacerbates degeneration of auditory neurons in kanamycin-induced ototoxicity in mice

Suppressive effect of pseudolaric acid B on Echinococcus multilocularis involving regulation of TGF-β1 signaling in vitro and in vivo

Targeted therapeutics and novel signaling pathways in non-alcohol-associated fatty liver/steatohepatitis (NAFL/NASH)

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