Growth differentiation factor-15/macrophage inhibitory cytokine-1 induction after kidney and lung injury.
The immunoregulatory cytokine macrophage inhibitory cytokine-1 (MIC-1), a divergent TGF-beta family member, and its murine ortholog, growth/differentiation factor-15 (GDF-15) are induced in hepatocytes by surgical and chemical injury and heat shock. To better understand the in vivo role this factor plays in organ injury, we examined the regulation of GDF-15 in murine models of kidney and lung injury. We demonstrate herein induction of GDF-15/MIC-1 after surgical, toxic/genotoxic, ischemic, and hyperoxic kidney or lung injury. Gdf15 induction was independent of protein synthesis, a hallmark of immediate-early gene regulation. Although TNF induced GDF-15 expression, injury-elicited Gdf15 expression was not reduced in mice deficient for both TNF receptor subtype. Furthermore, although the stress sensor p53 is known to induce GDF-15/MIC-1 expression, injury-elicited Gdf15 expression was unchanged in p53-null mice. Our results demonstrate that GDF-15 induction after organ injury is a hallmark of many tissues. These data demonstrate that GDF-15/MIC-1 is an early mediator of the injury response in kidney and lung that might regulate inflammation, cell survival, proliferation, and apoptosis in a variety of injured tissues and disease processes.
Zimmers
Teresa A
TA
DeWitt Daughtry Department of Surgery and Sylvester Comprehensive Cancer Center, University of Miami School of Medicine, Miami 33136, USA.
Jin
Xiaoling
X
Hsiao
Edward C
EC
McGrath
Sharon A
SA
Esquela
Aurora F
AF
Koniaris
Leonidas G
LG
D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D016207:Cytokines / Q000378:metabolism / Q000502:physiology*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D055436:Growth Differentiation Factor 15; D022781:Hepatocytes / Q000378:metabolism; D006358:Hot Temperature; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D007249:Inflammation; D007668:Kidney / Q000293:injuries* / Q000378:metabolism / Q000473:pathology; D008168:Lung / Q000378:metabolism / Q000473:pathology; D055370:Lung Injury; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011061:Poly A / Q000378:metabolism; D012313:RNA / Q000378:metabolism; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D016207:Cytokines; C526141:Gdf15 protein, mouse; D055436:Growth Differentiation Factor 15; D016212:Transforming Growth Factor beta; D016159:Tumor Suppressor Protein p53; D011061:Poly A; D012313:RNA