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STAT3 signaling within hepatocytes is required for anemia of inflammation in vivo

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Abstract

Background

Anemia of inflammation, commonly observed in patients with chronic diseases, is associated with decreased serum iron. Hepcidin, mainly produced by hepatocytes in a STAT3- and/or SMAD-dependent manner, is involved in iron homeostasis. What remains to be established is whether or not the hepatic IL-6/STAT3 signal has a role in anemia of inflammation in vivo.

Methods

Turpentine oil was subcutaneously injected into wild-type mice or hepatocyte-specific STAT3-deficient mice (L-STAT3KO) to induce inflammation.

Results

Turpentine injection increased serum IL-6 levels. It activated liver STAT3 in wild-type mice, but not in L-STAT3KO mice. In chronic inflammation, wild-type mice showed decreased serum iron levels and anemia with up-regulation of hepcidin levels in the liver. In contrast, L-STAT3KO mice showed no increase in hepatic hepcidin levels or anemia.

Conclusions

Liver STAT3 is critically involved in the development of anemia of inflammation via the expression of hepcidin. The liver regulates anemia of inflammation through STAT3 signaling.

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Acknowledgments

We thank Dr. S. Akira and Dr. K. Takeda for providing STAT3 floxed mice. This work was supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology, Japan.

Conflict of interest statement

No conflicts of interest exist.

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Authors and Affiliations

  1. Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka, 565-0871, Japan

    Ryotaro Sakamori, Tetsuo Takehara, Tomohide Tatsumi, Minoru Shigekawa, Hayato Hikita, Naoki Hiramatsu, Tatsuya Kanto & Norio Hayashi

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  1. Ryotaro Sakamori
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  2. Tetsuo Takehara
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  3. Tomohide Tatsumi
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  4. Minoru Shigekawa
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  5. Hayato Hikita
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  6. Naoki Hiramatsu
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  7. Tatsuya Kanto
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  8. Norio Hayashi
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Correspondence to Norio Hayashi.

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Sakamori, R., Takehara, T., Tatsumi, T. et al. STAT3 signaling within hepatocytes is required for anemia of inflammation in vivo. J Gastroenterol 45, 244–248 (2010). https://doi.org/10.1007/s00535-009-0159-y

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  • DOI: https://doi.org/10.1007/s00535-009-0159-y

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