TY - JOUR
T1 - RNA binding protein IGF2BP2 expression is induced by stress in the heart and mediates dilated cardiomyopathy
AU - Krumbein, Miriam
AU - Oberman, Froma
AU - Cinnamon, Yuval
AU - Golomb, Mordechai
AU - May, Dalit
AU - Vainer, Gilad
AU - Belzer, Vitali
AU - Meir, Karen
AU - Fridman, Irina
AU - Haybaeck, Johannes
AU - Poelzl, Gerhard
AU - Kehat, Izhak
AU - Beeri, Ronen
AU - Kessler, Sonja M.
AU - Yisraeli, Joel K.
N1 - Publisher Copyright:
© 2023, The Author(s).
PY - 2023/12/5
Y1 - 2023/12/5
N2 - The IGF2BP family of RNA binding proteins consists of three paralogs that regulate intracellular RNA localization, RNA stability, and translational control. Although IGF2BP1 and 3 are oncofetal proteins, IGF2BP2 expression is maintained in many tissues, including the heart, into adulthood. IGF2BP2 is upregulated in cardiomyocytes during cardiac stress and remodeling and returns to normal levels in recovering hearts. We wondered whether IGF2BP2 might play an adaptive role during cardiac stress and recovery. Enhanced expression of an IGF2BP2 transgene in a conditional, inducible mouse line leads to dilated cardiomyopathy (DCM) and death within 3-4 weeks in newborn or adult hearts. Downregulation of the transgene after 2 weeks, however, rescues these mice, with complete recovery by 12 weeks. Hearts overexpressing IGF2BP2 downregulate sarcomeric and mitochondrial proteins and have fragmented mitochondria and elongated, thinner sarcomeres. IGF2BP2 is also upregulated in DCM or myocardial infarction patients. These results suggest that IGF2BP2 may be an attractive target for therapeutic intervention in cardiomyopathies.
AB - The IGF2BP family of RNA binding proteins consists of three paralogs that regulate intracellular RNA localization, RNA stability, and translational control. Although IGF2BP1 and 3 are oncofetal proteins, IGF2BP2 expression is maintained in many tissues, including the heart, into adulthood. IGF2BP2 is upregulated in cardiomyocytes during cardiac stress and remodeling and returns to normal levels in recovering hearts. We wondered whether IGF2BP2 might play an adaptive role during cardiac stress and recovery. Enhanced expression of an IGF2BP2 transgene in a conditional, inducible mouse line leads to dilated cardiomyopathy (DCM) and death within 3-4 weeks in newborn or adult hearts. Downregulation of the transgene after 2 weeks, however, rescues these mice, with complete recovery by 12 weeks. Hearts overexpressing IGF2BP2 downregulate sarcomeric and mitochondrial proteins and have fragmented mitochondria and elongated, thinner sarcomeres. IGF2BP2 is also upregulated in DCM or myocardial infarction patients. These results suggest that IGF2BP2 may be an attractive target for therapeutic intervention in cardiomyopathies.
UR - http://www.scopus.com/inward/record.url?scp=85178473965&partnerID=8YFLogxK
U2 - 10.1038/s42003-023-05547-x
DO - 10.1038/s42003-023-05547-x
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C2 - 38052926
AN - SCOPUS:85178473965
SN - 2399-3642
VL - 6
JO - Communications Biology
JF - Communications Biology
IS - 1
M1 - 1229
ER -