Wnt/Chemerin Signaling Involved in Exercise Training Preventing Diaphragm Dysfunction Induced by Cigarette Smoke.

Area of Science:

• Respiratory Physiology
• Cellular Biology
• Exercise Science

Background:

• Cigarette smoke (CS) exposure induces diaphragm dysfunction, a critical respiratory muscle impairment.
• The roles of Wnt and Chemerin signaling pathways in CS-induced diaphragm dysfunction are not fully understood.

Purpose of the Study:

• To investigate if exercise training alleviates CS-induced diaphragm dysfunction.
• To determine the involvement of Wnt and Chemerin signaling pathways in this process.

Main Methods:

• C2C12 myoblasts were subjected to mechanical stretching and lipopolysaccharide treatment.
• Wild-type and CMKLR1 knockout mice were exposed to CS, followed by treadmill exercise training.
• Wnt/β-catenin agonist (LiCl) and antagonist (XAV939) were administered during exercise training.
• Diaphragm strength and fiber cross-sectional area were assessed.

Main Results:

• Mechanical stretching reduced inflammation and CMKLR1 expression in myoblasts.
• CMKLR1 knockout mice exhibited less diaphragm dysfunction after CS exposure.
• Combined LiCl and exercise training improved diaphragm strength and reduced IL-1β levels.
• Combined XAV939 and exercise training decreased chemerin protein levels.

Conclusions:

• Exercise training mitigates CS-induced diaphragm dysfunction by downregulating inflammation.
• The Wnt and Chemerin signaling pathways are key modulators in this exercise-induced improvement.
• Targeting these pathways alongside exercise may offer therapeutic benefits for respiratory muscle dysfunction.