4.7 Article

BMP-7 functions as a novel hormone to facilitate liver regeneration

Journal

FASEB JOURNAL
Volume 21, Issue 1, Pages 256-264

Publisher

FEDERATION AMER SOC EXP BIOL
DOI: 10.1096/fj.06-6837com

Keywords

transforming growth factor beta; hepatocytes

Funding

  1. NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [P01AI053194] Funding Source: NIH RePORTER
  2. NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [K08DK074558, R01DK061688] Funding Source: NIH RePORTER
  3. NIAID NIH HHS [AI53194] Funding Source: Medline
  4. NIDDK NIH HHS [DK55001, 1K08DK074558-01, DK61688] Funding Source: Medline

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Bone morphogenic protein-7 (BMP-7) is a key protein involved in liver organogenesis and development. The physiological circulating concentration of BMP-7 is between 100 and 300 pg/ml. BMP-7 expression is absent in the liver, but the receptors for BMP-7 are present on adult hepatocytes. Therefore, we hypothesized that BMP-7 might function as an endogenous regulator of adult hepatocyte proliferation and liver homeostasis. Here, we demonstrate that neutralization of circulating endogenous BMP-7 results in significantly impaired regeneration of the liver after partial hepatectomy. Therapeutic administration of recombinant human BMP-7 (rhBMP-7) significantly enhances liver regeneration associated with accelerated improvement of liver function. Collectively, our results argue for the role of BMP-7 as a kidney- and bone-produced endogenous regulator of hepatocyte health.

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