BMC biology · 2025
Brain miR-137 governs growth and development via GH/IGF-1 signaling.
СтатьяНазвание и аннотация: Перевод в очереди
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Liao Keng-Mao, Hsu Wei-Lun, Huang Wan-Yi, Luo Wei-Jia, Chang Jung-Hsuan, Yu Sung-Liang, Yang Pan-Chyr, Su Kang-Yi
Аннотация
BACKGROUND: Brain-enriched miR-137 is highly associated with neuropsychiatric disorders and neural development. Although complete loss of miR-137 that leads to postnatal lethality had been addressed in mice, the underlying mechanism particularly related to growth and development remains unknown.
RESULTS: MiR-137-deficient mice (Mir137-/-) exhibited postnatal lethality, severe growth retardation, osteoporosis, fat atrophy, and hypothermia. Despite comparable serum growth hormone (GH) levels, IGF-1 levels in both liver and serum were significantly reduced, with compensatory upregulation of IGF-1 receptor expression in major organs. Reduced IGF-1 levels were not due to defects in GH secretion by the pituitary nor GH responsiveness of hepatocytes. Instead, impaired in vivo GH-induced p-STAT5 signaling suggested GH resistance in Mir137-/-. Conditional deletion of Mir137 in the nervous system, but not in the liver, showed similar results, confirming the brain-specific role of miR-137. Transcriptomic analyses revealed that differentially expressed genes in the brain were enriched in development and neurogenesis while those in the liver showed diverse and less enrichments. IGF-1 reduction caused by miR-137 deficiency emerged as a central factor impacting the cell proliferation network to systemic growth.
CONCLUSIONS: This study underscores the critical role of miR-137 in failure to thrive through regulation of the GH/IGF-1 axis and supports the use of MiR137-/- as a disease model for GH resistance. Given the conserved miR-137 sequences between mice and humans, further human studies or clinical trials may validate its potential as a biomarker and therapeutic target for growth retardation.
RESULTS: MiR-137-deficient mice (Mir137-/-) exhibited postnatal lethality, severe growth retardation, osteoporosis, fat atrophy, and hypothermia. Despite comparable serum growth hormone (GH) levels, IGF-1 levels in both liver and serum were significantly reduced, with compensatory upregulation of IGF-1 receptor expression in major organs. Reduced IGF-1 levels were not due to defects in GH secretion by the pituitary nor GH responsiveness of hepatocytes. Instead, impaired in vivo GH-induced p-STAT5 signaling suggested GH resistance in Mir137-/-. Conditional deletion of Mir137 in the nervous system, but not in the liver, showed similar results, confirming the brain-specific role of miR-137. Transcriptomic analyses revealed that differentially expressed genes in the brain were enriched in development and neurogenesis while those in the liver showed diverse and less enrichments. IGF-1 reduction caused by miR-137 deficiency emerged as a central factor impacting the cell proliferation network to systemic growth.
CONCLUSIONS: This study underscores the critical role of miR-137 in failure to thrive through regulation of the GH/IGF-1 axis and supports the use of MiR137-/- as a disease model for GH resistance. Given the conserved miR-137 sequences between mice and humans, further human studies or clinical trials may validate its potential as a biomarker and therapeutic target for growth retardation.