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Regulation of the expression of follistatin in rat hepatocytes
Abstract
To elucidate the regulation of follistatin production in the liver, we studied changes in steady-state follistatin mRNA levels in cultured rat hepatocytes. Activin A stimulated follistatin mRNA levels in a time- and concentration-dependent manner. The stimulatory effect of activin A on follistatin mRNA was significant at 2 h, maximal at 6 h and declined thereafter. Incubating the cells with EGF increased follistatin mRNA levels at 48 h and later. The EGF-induced increase in follistatin mRNA was markedly inhibited by exogenous follistatin in the culture medium, which blocks the action of activin A synthesized in hepatocytes, suggesting that endogenous activin A at least partly mediated the effect of EGF. We also examined the effects of transforming growth factor-beta (TGF-beta), glucagon and alpha-adrenergic agonist, phenylephrine, on follistatin mRNA levels. TGF-beta increased the follistatin mRNA to levels similar to those caused by activin A. Phenylephrine and glucagon also increased follistatin mRNA levels but the effects were transient and weaker than those caused by activin A. Finally, follistatin mRNA levels were markedly increased in remnant liver 3 h after 70% hepatectomy. The mRNA remained elevated for up to 72 h. These results indicate that the expression of mRNA for follistatin is positively controlled by activin A, TGF-beta and other hormones or neurotransmitters. The stimulatory effect of EGF on follistatin mRNA is mediated by activin A released from hepatocytes.
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The liver is a key contributor to circulating levels of FST in humans.
“recent work indicated that the liver is a key contributor to circulating levels of FST in humans [[188], [189], [190]].”
From Hepatokines and metabolism: Deciphering communication from the liver (2021) · cites this paper as [189]
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Metadata
- Authors
- Zhang, Y.-Q., Kanzaki, M., Shibata, H., & Kojima, I.
- Affiliations
- Gunma University (JP)
- Corresponding author
- Kojima, Itaru
- Venue
- Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression
- Publisher
- Elsevier BV
- Published
- 1997-11
- Volume
- 1354
- Issue
- 3
- Pages
- 204-210
- ISSN
- 0167-4781 (ISSN-L)
- OpenAlex
- W2006511292
- Cited by
- 36
- References
- 27
- Citations by year
- 2023: 2 · 2021: 1 · 2020: 2 · 2019: 1 · 2017: 1 · 2016: 4 · 2015: 2
- FWCI
- 0.87
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Education, Culture, Sports, Science and Technology
- Topics
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
- Keywords
- follistatin, hepatocytes, activin A, TGF-beta, epidermal growth factor, glucagon, phenylephrine, hepatectomy, liver regeneration, gene expression regulation
- MeSH terms
- Animals, Cells, Cultured, Dose-Response Relationship, Drug, Epidermal Growth Factor, Gene Expression Regulation, Glucagon, Glycoproteins, Growth Substances, Inhibins, Liver, Male, Phenylephrine, RNA, Messenger, Time Factors, Transforming Growth Factor beta, Rats, Wistar, Activins, Follistatin, Rats
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