Table 1 Core and contextual genes dysregulated in the DMD^mdx rat model.

Core Gene

Dmd

-1.2

Dystrophin protein; structural anchor

Membrane integrity

Gene therapy (e.g., exon skipping, AAV-based delivery), stop codon readthrough

²⁴

Actc1

-2.7

Actin isoform; sarcomeric structure

Actin cytoskeleton

Targeting sarcomere stabilization to support contractile apparatus

Actn1

-1.0

Z-disc actin cross-linker

Cytoskeletal integrity

Stabilizing cytoskeleton; potential biomarker for sarcomere disorganization

Myh3

-4.4

Embryonic myosin; regeneration marker

Muscle repair

Myogenic regeneration enhancement (e.g., myosin-targeted therapies)

Myh8

-4.3

Perinatal myosin; regenerating muscle

Regeneration

Stimulating expression may enhance myogenic regeneration

Igf1

-1.3

Growth factor for satellite cell activation

PI3K/AKT signaling

IGF1-based therapies or agonists to enhance muscle regeneration

^54,57

Col6a1

-1.7

ECM collagen VI

ECM structure, fibrosis

Antifibrotic therapies; gene reactivation to restore ECM resilience

^{50]– [51}

Mmp2

-1.4

ECM degradation enzyme

ECM turnover, fibrosis

Balanced activation to reduce fibrosis and promote remodeling

^50,62

Tgfβ1

-1.3

Pro-fibrotic cytokine

Fibrosis, inflammation

Anti-TGFβ therapies to reduce fibrosis and improve regeneration

³³

Akt3

-0.7

PI3K/AKT pathway kinase

Cell survival, redox homeostasis

Activation may protect against oxidative stress and promote muscle repair

^58,69

Rock1

-1.02

Cytoskeletal regulator

Cytoskeleton remodeling

ROCK inhibitors may reduce fibrosis and cytoskeletal disorganization

^{58]– [59}

Pdgfra

-1.63

Fibro/adipogenic progenitor regulator

Fibrosis initiation

Anti-PDGFRα therapies to suppress fibroblast activation

⁵⁹

Contextual Gene

Myh6

1.89

Cardiac myosin; maladaptive shift

Cardiac gene expression

May indicate compensatory remodeling; monitor to avoid cardiac burden

Tbx5

3.03

Cardiac transcription factor

Cardiac activation

Possible off-target effect of compensatory expression in skeletal muscle

⁵⁶

Egfr

-0.9

Growth/survival receptor

PI3K/AKT, MAPK

EGFR modulation could restore muscle growth capacity

⁵⁸

Col1a1

-2.09

Fibrillar collagen; ECM structural support

Fibrosis, ECM integrity

Anti-fibrotic therapy targeting collagen production in early-stage disease

⁶¹

Col1a2

-2.03

Partner of Col1a1; contributes to ECM rigidity

Fibrosis

Anti-fibrotic therapy targeting collagen production

⁶¹

Mmp10

4.22

ECM degradation

ECM remodeling

May serve as biomarker for active tissue remodeling/fibrosis

⁶²

Keap1

0.54

NRF2 inhibitor; suppresses antioxidant response

Redox imbalance, oxidative stress

NRF2 activators could counter oxidative damage by inhibiting Keap1

Tnfrsf19

3.24

TNF receptor; inflammation driver

TNF signaling

TNF blockers may mitigate inflammatory tissue damage

⁷⁴

Dkk1

4.48

Wnt pathway inhibitor

Wnt signaling, regeneration

Wnt agonists could restore regenerative signaling impaired by Dkk1

⁷⁵

Nos2

1.45

iNOS; reactive nitrogen species production

Inflammation, oxidative stress

NOS2 inhibitors may reduce nitrosative stress and tissue injury

Fn1

-1.13

ECM adhesion protein

ECM remodeling

Enhancing fibronectin levels may aid in ECM repair

⁷²

Lgals3

-2.3

Immune modulation

Immune cell recruitment

Galectin-3 supplementation or mimetics may restore immune function

⁸⁴

Cd44

-1.8

Cell adhesion

Immune interaction

Therapeutic relevance in modulating inflammatory cell infiltration

⁸⁵

Atp2b2

1.91

Ca²⁺ ATPase; calcium extrusion

Calcium homeostasis

Upregulation may reflect protective adaptation; target for calcium overload modulation

⁷⁹

Atp1a2

0.91

Na⁺/K⁺-ATPase subunit

Calcium/ion regulation

May act as a compensatory marker; maintaining ionic balance

⁷⁹

Coro1a

-0.84

Actin regulator in immune cells

Immune motility, inflammation

Targeting Coro1a could improve immune cell dynamics and reduce chronic inflammation

⁷⁶