Time-course and muscle-specific gene expression of matrix metalloproteinases and inflammatory cytokines in response to acute treadmill exercise in rats

Mol Biol Rep. 2024 May 23;51(1):667. doi: 10.1007/s11033-024-09637-9.

Abstract

Background: The extracellular matrix (ECM) of skeletal muscle plays a pivotal role in tissue repair and growth, and its remodeling tightly regulated by matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), and inflammatory cytokines. This study aimed to investigate changes in the mRNA expression of MMPs (Mmp-2 and Mmp-14), TIMPs (Timp-1 and Timp-2), and inflammatory cytokines (Il-1β, Tnf-α, and Tgfβ1) in the soleus (SOL) and extensor digitorum longus (EDL) muscles of rats following acute treadmill exercise. Additionally, muscle morphology was examined using hematoxylin and eosin (H&E) staining.

Methods and results: Male rats were subjected to acute treadmill exercise at 25 m/min for 60 min with a %0 slope. The mRNA expression of ECM components and muscle morphology in the SOL and EDL were assessed in both sedentary and exercise groups at various time points (immediately (0) and 1, 3, 6, 12, and 24 h post-exercise). Our results revealed a muscle-specific response, with early upregulation of the mRNA expression of Mmp-2, Mmp-14, Timp-1, Timp-2, Il-1β, and Tnf-α observed in the SOL compared to the EDL. A decrease in Tgfβ1 mRNA expression was evident in the SOL at all post-exercise time points. Conversely, Tgfβ1 mRNA expression increased at 0 and 3 h post-exercise in the EDL. Histological analysis also revealed earlier cell infiltration in the SOL than in the EDL following acute exercise.

Conclusions: Our results highlight how acute exercise modulates ECM components and muscle structure differently in the SOL and EDL muscles, leading to distinct muscle-specific responses.

Keywords: Acute exercise; Gene expression; Inflammatory cytokines; Matrix metalloproteinases; Skeletal muscle.

MeSH terms

  • Animals
  • Cytokines* / genetics
  • Cytokines* / metabolism
  • Extracellular Matrix / metabolism
  • Gene Expression Regulation
  • Interleukin-1beta / genetics
  • Interleukin-1beta / metabolism
  • Male
  • Matrix Metalloproteinase 14 / genetics
  • Matrix Metalloproteinase 14 / metabolism
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinases* / genetics
  • Matrix Metalloproteinases* / metabolism
  • Muscle, Skeletal* / metabolism
  • Physical Conditioning, Animal* / physiology
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Tissue Inhibitor of Metalloproteinase-1 / genetics
  • Tissue Inhibitor of Metalloproteinase-1 / metabolism
  • Tissue Inhibitor of Metalloproteinase-2 / genetics
  • Tissue Inhibitor of Metalloproteinase-2 / metabolism
  • Transforming Growth Factor beta1 / genetics
  • Transforming Growth Factor beta1 / metabolism
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Cytokines
  • Matrix Metalloproteinases
  • Matrix Metalloproteinase 2
  • Tumor Necrosis Factor-alpha
  • Interleukin-1beta
  • RNA, Messenger
  • Tissue Inhibitor of Metalloproteinase-1
  • Transforming Growth Factor beta1
  • Tissue Inhibitor of Metalloproteinase-2
  • Matrix Metalloproteinase 14