Brain miR-137 governs growth and development via GH/IGF-1 signaling.
Journal
BMC biology
Journal Volume
23
Journal Issue
1
Start Page
Article number 197
ISSN
1741-7007
Date Issued
2025-07-01
Author(s)
Liao, Keng-Mao
Hsu, Wei-Lun
Huang, Wan-Yi
Luo, Wei-Jia
Chang, Jung-Hsuan
Abstract
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.
Subjects
GH resistance
Growth retardation
IGF-1
Knockout mice
MiR-137
Type
journal article