Endothelial transcription factor KLF2 negatively regulates liver regeneration via induction of activin A

Yosif Manavski, Tobias Abel, Junhao Hu, Dina Kleinlützum, Christian J. Buchholz, Christina Belz, Hellmut G. Augustin, Reinier A. Boon, Stefanie Dimmeler

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Endothelial cells (ECs) not only are important for oxygen delivery but also act as a paracrine source for signals that determine the balance between tissue regeneration and fibrosis. Here we show that genetic inactivation of flow-induced transcription factor Krüppel-like factor 2 (KLF2) in ECs results in reduced liver damage and augmentation of hepatocyte proliferation after chronic liver injury by treatment with carbon tetrachloride (CCl4). Serum levels of GLDH3 and ALT were significantly reduced in CCl4-treated EC-specific KLF2-deficient mice. In contrast, transgenic overexpression of KLF2 in liver sinusoidal ECs reduced hepatocyte proliferation. KLF2 induced activin A expression and secretion from endothelial cells in vitro and in vivo, which inhibited hepatocyte proliferation. However, loss or gain of KLF2 expression did not change capillary density and liver fibrosis, but significantly affected hepatocyte proliferation. Taken together, the data demonstrate that KLF2 induces an antiproliferative secretome, including activin A, which attenuates liver regeneration.

Original languageEnglish
Pages (from-to)3993-3998
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume114
Issue number15
DOIs
Publication statusPublished - 11 Apr 2017

Cite this

Manavski, Yosif ; Abel, Tobias ; Hu, Junhao ; Kleinlützum, Dina ; Buchholz, Christian J. ; Belz, Christina ; Augustin, Hellmut G. ; Boon, Reinier A. ; Dimmeler, Stefanie. / Endothelial transcription factor KLF2 negatively regulates liver regeneration via induction of activin A. In: Proceedings of the National Academy of Sciences of the United States of America. 2017 ; Vol. 114, No. 15. pp. 3993-3998.
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Endothelial transcription factor KLF2 negatively regulates liver regeneration via induction of activin A. / Manavski, Yosif; Abel, Tobias; Hu, Junhao; Kleinlützum, Dina; Buchholz, Christian J.; Belz, Christina; Augustin, Hellmut G.; Boon, Reinier A.; Dimmeler, Stefanie.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 114, No. 15, 11.04.2017, p. 3993-3998.

Research output: Contribution to journalArticleAcademicpeer-review

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AU - Manavski, Yosif

AU - Abel, Tobias

AU - Hu, Junhao

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AU - Buchholz, Christian J.

AU - Belz, Christina

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