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Published online before print November 20, 2006 as doi: 10.1096/fj.06-6837com.

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

Hikaru Sugimoto, Changqing Yang, Valerie S. LeBleu, Mary A. Soubasakos, Mauricio Giraldo, Michael Zeisberg, and Raghu Kalluri

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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