What question did this study set out to answer?

The study aims to investigate the role of secretoglobin 3A1 in muscle satellite cell differentiation and fiber type regeneration following injury.

January 10, 2026Cellular and Molecular Life Sciences0 citationsOpen Access

Secretoglobin 3A1 in activated muscle satellite cells contributes to myosin heavy chain IIX and IIB fiber differentiation

SYShigetoshi YokoyamaPennsylvania State University TKTaketomo Kido MYMitsuhiro YonedaUniversity of Nagasaki

Key Result

SCGB3A1 is essential for IIX and IIB fiber regeneration, with Scgb3a1-null mice showing reduced fiber size and compromised muscle performance compared to wild-type.

Key Points

The study aims to investigate the role of secretoglobin 3A1 in muscle satellite cell differentiation and fiber type regeneration following injury.
Lineage tracing of SCGB3A1 in mice to track cell contribution to muscle regeneration.
Comparison of muscle regeneration in Scgb3a1-null and conditional-null mice.
Assessment of muscle fiber size and performance in aged Scgb3a1-null mice.
SCGB3A1 is induced post-muscle injury and is present in muscle satellite cells.
Scgb3a1-null mice show impaired IIX and IIB muscle fiber regeneration.
Aged Scgb3a1-null mice have smaller muscle fibers and reduced muscle mass, affecting performance.

Structured PICO

Population

Preclinical models including Scgb3a1-null (Scgb3a1-/-) mice on C57BL/6NCr background, Pax7CreERT2;Scgb3a1f/f conditional-null mice, Scgb3a1GFP knock-in mice, Scgb3a1CreERT2;mT/mG mice, and C2C12 myogenic cell lines.

Intervention

Genetic deletion of Scgb3a1 (global knockout or satellite cell-specific conditional knockout via tamoxifen) and BaCl2-induced skeletal muscle injury.

Comparator

Age-matched wild-type (Scgb3a1+/+) mice, oil-injected Pax7CreERT2;Scgb3a1f/f mice, and uninjured muscle.

Outcome

Skeletal muscle fiber regeneration, specifically MyHC-IIX and IIB fiber differentiation, fiber size, and muscle performance.surrogate

SCGB3A1 is a novel molecule expressed in activated muscle satellite cells that regulates Notch3 expression and is essential for fiber-type specific skeletal muscle regeneration and maintenance of muscle mass during aging.

Main Result

Absolute Event Rate: 0% vs 0%

Abstract

Abstract Skeletal muscle has an innate ability to restore damaged muscle fibers by contributing specific progenitor cells, called muscle satellite cells. Here we show that secretoglobin (SCGB) 3A1, a tumor suppressor gene in various malignancies including rhabdomyosarcoma, is induced just after muscle injury and contributes to damaged muscle fiber regeneration. Lineage tracing of SCGB3A1 in mice show that SCGB3A1-positive cells highly express myosin heavy chain (MyHC)-IIX in damaged fiber area. Scgb3a1 -null and Pax7 CreERT2 ; Scgb3a1 f/f conditional-null mice exhibit defective IIX and IIB fiber regeneration, with a concomitant reduction in the expression of Notch3 , a gene important for the maintenance of satellite cell self-renewal pools. Aged Scgb3a1 -null mice show reduced size of muscle fibers and mass, resulting in compromised muscle performance as compared to the age-matched wild-type mice. This study reveals that SCGB3A1 is an unexpected novel molecule expressed in muscle satellite cells that contributes to fiber type specific muscle regeneration.

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