The transcription factor Prox1 is essential for satellite cell differentiation and muscle fibre-type regulation.

The remarkable adaptive and regenerative capacity of skeletal muscle is regulated by several transcription factors and pathways. Here we show that the transcription factor Prox1 is an important regulator of myoblast differentiation and of slow muscle fibre type. In both rodent and human skeletal muscles Prox1 is specifically expressed in slow muscle fibres and in muscle stem cells called satellite cells. Prox1 activates the NFAT signalling pathway and is necessary and sufficient for the maintenance of the gene program of slow muscle fibre type. Using lineage-tracing we show that Prox1-positive satellite cells differentiate into muscle fibres. Furthermore, we provide evidence that Prox1 is a critical transcription factor for the differentiation of myoblasts via bi-directional crosstalk with Notch1. These results identify Prox1 as an essential transcription factor that regulates skeletal muscle phenotype and myoblast differentiation by interacting with the NFAT and Notch pathways.

MicroRNA expression and protein acetylation pattern in respiratory and limb muscles of Parp-1(-/-) and Parp-2(-/-) mice with lung cancer cachexia.

BACKGROUND: Current treatment options for cachexia, which impairs disease prognosis, are limited. Muscle-enriched microRNAs and protein acetylation are involved in muscle wasting including lung cancer (LC) cachexia. Poly(ADP-ribose) polymerases (PARP) are involved in muscle metabolism. We hypothesized that muscle-enriched microRNA, protein hyperacetylation, and expression levels of myogenic transcription factors (MTFs) and downstream targets, muscle loss and function improve in LC cachectic Parp-1(−/−) and Parp-2(−/−) mice. METHODS: Body and muscle weights, grip strength, muscle phenotype, muscle-enriched microRNAs (miR-1, -133, -206, and -486), protein acetylation, acetylated levels of FoxO1, FoxO3, and PGC-1α, histone deacetylases (HDACs) including SIRT1, MTFs, and downstream targets (α-actin, PGC-1α, and creatine kinase) were evaluated in diaphragm and gastrocnemius of LC (LP07 adenocarcinoma) wild type (WT), Parp-1(−/−) and Parp-2−/− mice. RESULTS: Compared to WT cachectic animals, in both respiratory and limb muscles of Parp-1(−/−) and Parp-2(−/−) cachectic mice: downregulation of muscle-specific microRNAs was counterbalanced especially in gastrocnemius of Parp-1(−/−) mice; increased protein acetylation was attenuated (improvement in HDAC3, SIRT-1, and acetylated FoxO3 levels in both muscles, acetylated FoxO1 levels in the diaphragm); reduced MTFs and creatine kinase levels were mitigated; body and muscle weights, strength, and muscle fiber sizes improved, while tumor weight and growth decreased. CONCLUSIONS: These molecular findings may explain the improvements seen in body and muscle weights, limb muscle force and fiber sizes in both Parp-1(−/−) and Parp-2(−/−) cachectic mice. GENERAL SIGNIFICANCE: PARP-1 and -2 play a role in cancer-induced cachexia, thus selective pharmacological inhibition of PARP-1 and -2 may be of interest in clinical settings.

Towards fabrication of 3D printed medical devices to prevent biofilm formation.

The use of three-dimensional (3D) printing technologies is transforming the way that materials are turned into functional devices. We demonstrate in the current study the incorporation of anti-microbial nitrofurantoin in a polymer carrier material and subsequent 3D printing of a model structure, which resulted in an inhibition of biofilm colonization. The approach taken is very promising and can open up new avenues to manufacture functional medical devices in the future.