Estrogen Stabilizes Interferon-Inducible Genes During Skeletal Muscle Regeneration

Area of Science:

• Muscle regeneration
• Inflammation and immunity
• Endocrinology

Background:

• Skeletal muscle repair relies on balanced inflammation.
• Estrogen and CD169+ macrophages are implicated in tissue repair.
• Interferon-inducible genes in muscle repair are understudied.

Purpose of the Study:

• Investigate the effect of 17β-estradiol on Siglec1 (CD169) expression and co-expression networks during muscle regeneration.
• Assess the role of estrogen in modulating inflammatory gene expression post-muscle injury.

Main Methods:

• Ovariectomized mice received 17β-estradiol or placebo, followed by muscle injury and simulated flight.
• Gene expression analysis and immunohistochemistry were performed at 32, 96, and 192 hours post-injury.
• Differential gene expression and correlation analyses identified transcriptional changes and gene network alterations.

Main Results:

• Siglec1 expression remained elevated in 17β-estradiol-treated mice at 192 hours post-injury, unlike in placebo mice.
• Siglec1 showed strong association with interferon genes under placebo, but this connectivity weakened with 17β-estradiol treatment.
• Immunohistochemistry confirmed increased CD169 protein in regenerating muscle of estrogen-treated mice.

Conclusions:

• Estrogen maintains more stable Siglec1 expression during muscle regeneration compared to an estrogen-deficient state.
• Estrogen deficiency may disrupt inflammatory signaling, potentially impairing muscle repair.
• Findings may guide interventions for muscle recovery in postmenopausal women.