thymosin-beta(4) and Wounds-and-Injuries

Thymosin β4 (Tβ4), a multifunctional peptide, has been used successfully in several clinical trials involving tissue repair and regeneration. The review will first update the current information on the common underlying cellular cascades and pathways that are basic to Tβ4's regenerative activity and second, on the current and potential uses of this protein in the clinic.. Significant advances in our understanding of the actions of Tβ4 have occurred in directing stem cell maturation and in regeneration and repair of injuries. Many of its activities directly affect the repair cascade following injury. Using PubMed, we summarize the discovery and isolation of Tβ4 as well as the studies on tissue repair, which have provided the scientific foundation for ongoing and projected trials in the treatment of eye injuries, dermal wounds, repair of the heart following myocardial infarction and healing of the brain following stroke, trauma or neurological diseases.. Based on its multifunctional activities during tissue regeneration in various animal studies, Tβ4 has the potential for new clinical applications such kidney and liver disease, as well as repair of spinal cord, bone and ligament damage. In addition, it may be useful in the treatment of a wide range of other applications, including the consequences of aging and viral infections.

Topics: Amino Acid Sequence; Animals; Epidermolysis Bullosa; Molecular Sequence Data; Pressure Ulcer; Regeneration; Spinal Cord; Thymosin; Varicose Ulcer; Wound Healing; Wounds and Injuries

Wound fluids were collected up to 60 h after abdominal surgery. Immediately after obtaining the wound fluid by Robinson drainage, wound fluid was centrifuged to remove blood cells and inflammatory cells. The concentration of total protein as well as of thymosin beta(4) was determined in the cell-free supernatant solution. Total protein concentration decreased from about 50 g/L to 30 g/L within 60 h after surgery. After surgery we observed a concentration of up to 20 mg thymosin beta(4) per liter decreasing to about 1 mg/L with time. Neither thymosin beta(10) nor oxidized thymosin beta(4) was detected in human wound fluid.

Topics: Abdomen; Chromatography, High Pressure Liquid; Humans; Postoperative Complications; Proteins; Surgical Procedures, Operative; Thymosin; Wounds and Injuries

The identification of in vivo secreted proteins is a major challenge in systems biology. Here we report a novel technique using capillary ultrafiltration (CUF) probes to identify the secreted proteins involved in wound healing. CUF probes, which use semipermeable membrane hollow fibers to continuously capture secreted proteins, were used to sample skin wound fluids. To identify low-abundance proteins, we digested the CUF probe-collected wound fluid with trypsin and then directly subjected it to MS without using 2-DE separation. Two protein fragments with masses of 1565.7 and 1694.8 Da were identified by MS as peptides of thymosin beta10 and beta4, respectively. This is the first identification of thymosin beta10 as an in vivo constituent of the skin wound fluid. The LKKTETQ peptide, a common actin-binding domain of thymosin beta4 and beta10, significantly enhanced skin wound healing in vitro and in vivo. Our data suggest that the enhancement of wound healing by LKKTETQ may be mediated by purinergic receptors. The technique of using CUF probes linked to mass spectrometric proteomics represents a powerful method to identify in vivo secreted proteins, and may be applicable for identification of proteins relevant in various human diseases.

Topics: Animals; Female; Histocytochemistry; Mass Spectrometry; Mice; Mice, Inbred BALB C; Molecular Weight; Proteins; Proteomics; Sequence Analysis, Protein; Skin; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Thymosin; Ultrafiltration; Wounds and Injuries

Topics: Acanthamoeba; Actins; Amino Acid Sequence; Animals; Carrier Proteins; Infections; Microfilament Proteins; Molecular Sequence Data; Protein Binding; Protozoan Proteins; Sequence Homology, Nucleic Acid; Thymosin; Vertebrates; Wounds and Injuries