Ec. Hsiao et al., Characterization of growth-differentiation factor 15, a transforming growth factor beta superfamily member induced following liver injury, MOL CELL B, 20(10), 2000, pp. 3742-3751
We have identified a new murine transforming growth factor beta superfamily
member, growth-differentiation factor 15 (Gdf15), that is expressed at hig
hest levels in adult liver. As determined by Northern analysis, the express
ion of Gdf15 in liver was rapidly and dramatically up-regulated following v
arious surgical and chemical treatments that cause acute liver injury and r
egeneration. In situ hybridization analysis revealed distinct patterns of G
df15 mRNA localization that appeared to reflect the known patterns of hepat
ocyte injury in each experimental treatment. In addition, treatment of two
hepatocyte-like cell lines with either carbon tetrachloride or heat shock i
nduced Gdf15 mRNA expression, indicating that direct cellular injury can in
duce Gdf15 expression in the absence of other cell types, such as inflammat
ory cells, In order to investigate the potential functions of Gdf15, we cre
ated Gdf15 null mice by gene targeting. Homozygous null mice were viable an
d fertile, Despite the dramatic regulation of Gdf15 expression observed in
the partial-hepatectomy and carbon tetrachloride injury models, we found no
differences in the injury responses between homozygous null mutants and wi
ld-type mice. Our findings suggest either that Gdf15 does not have a regula
tory role in liver injury and regeneration or that Gdf15 function within th
e liver is redundant with that of other signaling molecules.