Follistatin is well known as an inhibitor of transforming growth factor (TGF)-β superfamily ligands including myostatin and activin A. Myostatin, a negative regulator of muscle growth, is a promising target with which to treat muscle atrophic diseases. Here, we focused on the N-terminal domain (ND) of follistatin (Fst) that interacts with the type I receptor binding site of myostatin. Through bioassay of synthetic ND-derived fragment peptides, we identified DF-3, a new myostatin inhibitory 14-mer peptide which effectively inhibits myostatin, but fails to inhibit activin A or TGF-β1, in an in vitro luciferase reporter assay. Injected intramuscularly, DF-3 significantly increases skeletal muscle mass in mice and consequently, it can serve as a platform for development of muscle enhancement based on myostatin inhibition.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.bmcl.2019.126892 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
[Research progress on molecular mechanism related to skeletal muscle atrophy].
Sheng Li Xue Bao
December 2024
Department of Orthopaedics, the First Hospital of Lanzhou University, Lanzhou 730000, China.
The maintenance of skeletal muscle quality involves various signal pathways that interact with each other. Under normal physiological conditions, these intersecting signal pathways regulate and coordinate the hypertrophy and atrophy of skeletal muscles, balancing the protein synthesis and degradation of muscle. When the total rate of protein synthesis exceeds that of protein degradation, the muscle gradually becomes enlarged, while when the total rate of protein synthesis is lower than that of protein degradation, the muscle shrinks.
View Article and Find Full Text PDFInhibition of CILP2 Improves Glucose Metabolism and Mitochondrial Dysfunction in Sarcopenia via the Wnt Signalling Pathway.
J Cachexia Sarcopenia Muscle
December 2024
Shengli Clinical Medical College, Fujian Medical University, Fuzhou, People's Republic of China.
Background: Skeletal muscle is the primary organ involved in insulin-mediated glucose metabolism. Elevated levels of CILP2 are a significant indicator of impaired glucose tolerance and are predominantly expressed in skeletal muscle. It remains unclear whether CILP2 contributes to age-related muscle atrophy through regulating the glucose homeostasis and insulin sensitivity.
View Article and Find Full Text PDFAnti-Inflammatory Role of the Klotho Protein and Relevance to Aging.
Cells
August 2024
Department of Endocrinology and Metabolism, Huashan Hospital, Shanghai Medical School, Fudan University, Shanghai 200030, China.
Article Synopsis
- The α-Klotho protein, produced mainly in the kidneys and brain, is essential for regulating fibroblast growth factor 23 (FGF23) and is linked to several chronic age-related diseases like diabetes and Alzheimer's through its anti-inflammatory properties.
- * Klotho exists in two forms: a membrane-bound form and a soluble form (s-Klotho), which interacts with various growth factor receptors and regulates major pathways, although its exact mechanisms of action are still being studied.
- * Low levels of Klotho are associated with increased inflammation, muscle loss, and fibrotic diseases, but s-Klotho can counteract these effects by inhibiting inflammatory pathways and promoting muscle repair.
Diagnostic and predictive abilities of myokines in patients with heart failure.
Adv Protein Chem Struct Biol
July 2024
Department of Internal Medicine II, Division of Cardiology, Paracelsus Medical University, Salzburg, Austria. Electronic address:
Article Synopsis
- Myokines are a diverse group of proteins released by muscle cells that have various effects on the body, impacting communication between muscles and organs like the brain, liver, and fat tissues.
- They play crucial roles in processes such as muscle growth, inflammation, energy balance, and adaptation to exercise, while also being linked to many health conditions.
- Recent research has identified over 250 myokines, with some, like myostatin and interleukin-6, showing potential as biomarkers for heart failure and helping to predict disease progression.
Effects of exercise or metformin on myokine concentrations in patients with breast and colorectal cancer: A phase II multi-centre factorial randomized trial.
J Cachexia Sarcopenia Muscle
August 2024
Dana-Farber Cancer Institute, Boston, MA, USA.
Background: Physical activity and metformin pharmacotherapy are associated with improved clinical outcomes in breast and colorectal cancer survivors. Myokines are cytokines secreted from skeletal muscle that may mediate these associations.
Methods: This hypothesis-generating analysis used biospecimens collected from a multi-centre 2 × 2 factorial randomized design of 116 patients with stage I-III breast and colorectal cancer who were randomized to 12 weeks of (1) aerobic exercise (moderate intensity titrated to 220 min/week); (2) metformin (850 mg daily for 2 weeks and then titrated to 850 mg twice per day); (3) aerobic exercise and metformin; or (4) control.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!