Splice variant of STEAP4 localizes in the nucleus, making it a possible transcriptional regulator of IL-6 production

Ebe, Hiroshi; Matsumoto, Isao; Osada, Akira; Kurata, Izumi; Kawaguchi, Haruna; Kondo, Yuya; Tsuboi, Hiroto; Sumida, Takayuki

doi:10.1080/14397595.2018.1484415

Cited by 9 publications

(6 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Irrespective of our data, it is not certain yet the mechanism by which STAMP2 alter FPN expression at transcriptional level. Although it has been reported that a splice variant of STEAP4 (v‐STEAP4) localizes to the nucleus and acts as a transcriptional regulator, 48 it is not clear whether STAMP2 directly affects the FPN promoter. Further studies to clarify whether STAMP2 directly regulates the activity of FPN promotor or indirectly modulates the cross‐talk between STAMP2 and the hepcidin‐FPN axis are an urgent challenging future task.…”

Section: Discussionmentioning

confidence: 99%

Hepatic STAMP2 mediates recombinant FGF21‐induced improvement of hepatic iron overload in nonalcoholic fatty liver disease

Kim

Kwon

et al. 2020

FASEB j.

View full text Add to dashboard Cite

Although previous studies have shown that the administration of fibroblast growth factor 21 (FGF21) reverses hepatic steatosis, the mechanism by which FGF21 exerts a therapeutic effect on nonalcoholic fatty liver disease (NAFLD) is not yet entirely understood. We previously demonstrated that hepatic six transmembrane protein of prostate 2 (STAMP2) may represent a suitable target for NAFLD. We investigated the mechanism underlying the therapeutic effect of recombinant FGF21 on NAFLD, focusing on the involvement of hepatic STAMP2. In this study, we used human nonalcoholic steatosis patient pathology samples, C57BL/6 mice for a high‐fat diet (HFD)‐induced in vivo NAFLD model, and used human primary hepatocytes and HepG2 cells for oleic acid (OA)‐induced in vitro NAFLD model. We observed that recombinant FGF21 treatment ameliorated hepatic steatosis and insulin resistance through the upregulation of STAMP2 expression. We further observed hepatic iron overload (HIO) and reduced iron exporter, ferroportin expression in the liver samples obtained from human NAFLD patients, and HFD‐induced NAFLD mice and in OA‐treated HepG2 cells. Importantly, recombinant FGF21 improved HIO through the hepatic STAMP2‐mediated upregulation of ferroportin expression. Our data suggest that hepatic STAMP2 may represent a suitable therapeutic intervention target for FGF21‐induced improvement of NAFLD accompanying HIO.

show abstract

Section: Discussionmentioning

confidence: 99%

Hepatic STAMP2 mediates recombinant FGF21‐induced improvement of hepatic iron overload in nonalcoholic fatty liver disease

Kim

Kwon

et al. 2020

FASEB j.

View full text Add to dashboard Cite

show abstract

“…However, it is unclear whether the STAMP2‐induced decrease in ferroportin expression is hepcidin‐dependent or hepcidin‐independent. Although it has been reported that a splice variant of STEAP4 (v‐STEAP4) localizes to the nucleus and acts as a transcriptional regulator, 60 it is not clear whether STAMP2 directly affects the promoters of iron transporters such as ferroportin. Further studies to clarify whether STAMP2 directly regulates the promoter activity of iron promoters or indirectly modulates the cross‐talk between PCBs and the hepcidin‐FPN axis are an urgent challenging future task.…”

Section: Discussionmentioning

confidence: 99%

Hepatic STAMP2 alleviates polychlorinated biphenyl‐induced steatosis and hepatic iron overload in NAFLD models

Kim

Park

et al. 2022

Environmental Toxicology

View full text Add to dashboard Cite

Polychlorinated biphenyls (PCBs) have been associated with neurotoxicity, hepatoxicity, oncogenicity, and endocrine-disrupting effects. Although the recent studies have demonstrated that PCB exposure leads to nonalcoholic fatty liver disease (NAFLD), the underlying mechanism has remained unsolved. In this study, we examined the hepatic effects of a PCB mixture, Aroclor 1260, whose composition mimics human bioaccumulation patterns, and PCB 126 in C57BL/6 mice. Male C57Bl/6 mice were fed a standard diet or a 60% high-fat diet and exposed to Aroclor 1260 (10 mg/kg or 20 mg/kg) or PCB 126 (1 mg/kg or 5 mg/kg) by intraperitoneal injection for a total of four injections (2, 3, 4, and 5 weeks) for 6 weeks. In mice, both Aroclor 1260 and PCB 126-induced liver damage, hepatic steatosis and inflammation. We also observed that PCB exposure-induced hepatic iron overload (HIO). We previously demonstrated that hepatic six transmembrane protein of prostate 2 (STAMP2) may represent a suitable therapeutic target for NAFLD patients. Thus, we further examined whether hepatic STAMP2 is involved in PCB-induced NAFLD. We observed that hepatic STAMP2 was significantly decreased in PCB-induced NAFLD models in vivo and in vitro. Furthermore, overexpression of hepatic STAMP2 using an adenoviral delivery system resulted in improvement of PCB-induced steatosis and HIO in vivo and in vitro. Our findings indicate that enhancing hepatic STAMP2 expression represents a potential therapeutic avenue for the treatment of PCB exposure-induced NAFLD.

show abstract

“…The increased expression of metalloreductase proteins in the egg-injected mice bladder tissue may have implications for regulating the production of IL-6 (i.e. an increase) [ 72 ], where in parasitic diseases like schistosomiasis, an increase in IL-6 may promote Th2 differentiation and inhibit Th1 polarization [ 73 ]. In addition, the upregulation of Disabled homolog 2 ( Dab2 ) may facilitate Treg-mediated immunosuppression in response to infection; a downregulation of this protein has been linked with a pro-inflammatory switch [ 74 , 75 ].…”

Section: Discussionmentioning

confidence: 99%

Host tissue proteomics reveal insights into the molecular basis of Schistosoma haematobium-induced bladder pathology

et al. 2022

View full text Add to dashboard Cite

Urogenital schistosomiasis remains a major public health concern worldwide. In response to egg deposition, the host bladder undergoes gross and molecular morphological changes relevant for disease manifestation. However, limited mechanistic studies to date imply that the molecular mechanisms underlying pathology are not well-defined. We leveraged a mouse model of urogenital schistosomiasis to perform for the first time, proteome profiling of the early molecular events that occur in the bladder after exposure to S. haematobium eggs, and to elucidate the protein pathways involved in urogenital schistosomiasis-induced pathology. Purified S. haematobium eggs or control vehicle were microinjected into the bladder walls of mice. Mice were sacrificed seven days post-injection and bladder proteins isolated and processed for proteome profiling using mass spectrometry. We demonstrate that biological processes including carcinogenesis, immune and inflammatory responses, increased protein translation or turnover, oxidative stress responses, reduced cell adhesion and epithelial barrier integrity, and increased glucose metabolism were significantly enriched in S. haematobium infection. S. haematobium egg deposition in the bladder results in significant changes in proteins and pathways that play a role in pathology. Our findings highlight the potential bladder protein indicators for host-parasite interplay and provide new insights into the complex dynamics of pathology and characteristic bladder tissue changes in urogenital schistosomiasis. The findings will be relevant for development of improved interventions for disease control.

show abstract

Splice variant of STEAP4 localizes in the nucleus, making it a possible transcriptional regulator of IL-6 production

Cited by 9 publications

References 13 publications

Hepatic STAMP2 mediates recombinant FGF21‐induced improvement of hepatic iron overload in nonalcoholic fatty liver disease

Hepatic STAMP2 mediates recombinant FGF21‐induced improvement of hepatic iron overload in nonalcoholic fatty liver disease

Hepatic STAMP2 alleviates polychlorinated biphenyl‐induced steatosis and hepatic iron overload in NAFLD models

Host tissue proteomics reveal insights into the molecular basis of Schistosoma haematobium-induced bladder pathology

Contact Info

Product

Resources

About