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Ectopic TWEAKR expression in type I fiber of stroke-prone spontaneously hypertensive rats is related to slow muscle-specific hypotrophy
- Source :
- Life sciences. 237
- Publication Year :
- 2019
-
Abstract
- Aims Stroke-prone spontaneously hypertensive rats (SHRSP) show significantly lower body weight than normotensive Wistar-Kyoto rats (WKY). Our hypotheses are as follows: weight loss of the skeletal muscle is related to hypertension-related diseases, and muscle hypotrophy is useful as a therapeutic target for hypertension and hypertension-related diseases. In this study, we aimed to investigate the pathophysiological characteristics of muscle hypotrophy in SHRSP to determine the therapeutic target molecule(s). Main methods The difference in skeletal muscles in the lower leg between WKY and SHRSP was evaluated mainly through weight/tibial length, histological, gene expression, and protein expression analyses. Key findings SHRSP had a significantly lower weight/tibial length in soleus and gastrocnemius, but not in plantaris and tibialis anterior, indicating that muscles consisting of a relatively high amount of slow muscle fiber were affected. This result was confirmed by the histological analysis of soleus, showing that type I fiber mainly decreased the fiber size. Microarray and protein expression analyses showed that the muscle-specific ubiquitin ligase, muscle RING finger 1 (MuRF1), but not atrogin-1, was highly expressed in soleus, but not in plantaris, in SHRSP. TNF-like weak inducer of apoptosis receptor (TWEAKR) was predicted as a MuRF1 up-regulator by Ingenuity Pathway Analysis and immunostained only in type II fiber in WKY but in both type I and II fibers in SHRSP. Significance TWEAKR is a type II-specific receptor in the skeletal muscle. Ectopic TWEAKR expression in type I fiber of SHRSP is most likely involved in slow muscle-specific hypotrophy through MuRF1 overexpression.
- Subjects :
- 0301 basic medicine
Male
medicine.medical_specialty
Microarray
Ubiquitin-Protein Ligases
Muscle Fibers, Skeletal
Muscle Proteins
030226 pharmacology & pharmacy
Rats, Inbred WKY
General Biochemistry, Genetics and Molecular Biology
Muscle, Smooth, Vascular
Tripartite Motif Proteins
03 medical and health sciences
0302 clinical medicine
Internal medicine
Rats, Inbred SHR
Gene expression
medicine
Animals
Inducer
General Pharmacology, Toxicology and Pharmaceutics
Receptor
Muscle, Skeletal
biology
business.industry
Skeletal muscle
General Medicine
Pathophysiology
Ubiquitin ligase
Rats
Stroke
Muscular Atrophy
030104 developmental biology
medicine.anatomical_structure
Endocrinology
Apoptosis
TWEAK Receptor
Hypertension
biology.protein
business
Subjects
Details
- ISSN :
- 18790631
- Volume :
- 237
- Database :
- OpenAIRE
- Journal :
- Life sciences
- Accession number :
- edsair.doi.dedup.....0cb77697bf07de4296c43dc292210f51