Thymosin β4 Accelerates Wound Healing

Abstract

Angiogenesis is an essential step in the repair process that occurs after injury. In this study, we investigated whether the angiogenic thymic peptide thymosin beta4 (Tbeta4) enhanced wound healing in a rat full thickness wound model. Addition of Tbeta4 topically or intraperitoneally increased reepithelialization by 42% over saline controls at 4 d and by as much as 61% at 7 d post-wounding. Treated wounds also contracted at least 11% more than controls by day 7. Increased collagen deposition and angiogenesis were observed in the treated wounds. We also found that Tbeta4 stimulated keratinocyte migration in the Boyden chamber assay. After 4-5 h, migration was stimulated 2-3-fold over migration with medium alone when as little as 10 pg of Tbeta4 was added to the assay. These results suggest that Tbeta4 is a potent wound healing factor with multiple activities that may be useful in the clinic.

Ku80 as a Novel Receptor for Thymosin β4 That Mediates Its Intracellular Activity Different from G-actin Sequestering

“…Although it is a typical intracellular polypeptide, it plays numerous roles, both intracellularly and extracellularly. Numerous observations indicate that T␤4 is involved in adhesion and spreading of fibroblasts (1,2), differentiation of endothelial cells (3,4), directional migration of endothelial cells and keratinocytes (5)(6)(7)(8), angiogenesis (3-6, 9, 10), wound healing (6,7,11), hair follicle growth (8), and apoptosis (12,13), and has been described to possess anti-inflammatory properties (11,14). In addition, elevated T␤4 expression has been observed in various malignant cell lines and tumors (15)(16)(17) and its levels seem to be associated with increased tumorigenicity and metastatic potential (10, 13, 18 -20).…”

“…Thus, T␤4 externally added to endothelial cells: (a) induces expression and release of plasminogen activator inhibitor type 1 (PAI-1) by the mechanism involving activation of the mitogen-activated protein kinase cascade leading to enhanced c-Fos/c-Jun binding to the AP-1-like element present in the PAI-1 promoter (25,26); (b) binds to PINCH and integrinlinked kinase, resulting in activation of the survival kinase Akt, and thus promotes myocardial and endothelial cell migration in the embryonic heart (27) and (c) promotes skin and corneal wound healing through its effects on cell migration, angiogenesis, and possibly cell survival (4,6,11).…”

Thymosin β as an Actin-binding Protein with a Variety of Functions

“…Major activities which it exhibits are: actin binding, promotion of cell migration, angiogenesis, an anti-inflammatory and anti-apoptotic action, promoting wound healing, inhibition of fibrosis, stem cell recruitment and differentiation., protection from burns, cytotoxic agents and hypoxia [7,24,25,27,28,30,33]. It is worth noting that disturbances in the expression of this protein may have serious clinical consequences, particularly in the context of cancer [6,36,1,23].…”

Analysis of the Expression Patterns of Thymosin β4, Vascular Endothelial Growth Factor, and Hypoxia-Inducible Factor-1α in Various Tumors Using Tissue Microarray

“…사이모신 베타 4는 actin 과 결합하며 주로 F-actin을 G-actin으로 분리하는 actin depolymerization을 증가시키는 펩티드로서 actin cytoskeleton의 구조를 변경하는데 관여하여 직접적으로 세포의 이동을 조절 한다 [18]. 처음 사이모신 베타 4가 발견될 때는 갑상선에서 분 비되는 펩티드로써 면역반응이나 염증반응에도 관여하는 cytokine이나 성장인자일 것으로 알려졌으나 최근 여러 가지 연 구를 통해 혈관신생(angiogenesis)을 증가시키고 [3,13] 상처 치유(wound healing) [14,15]를 촉진하며 모발 성장(hair growth) 등을 증진시킨다고 보고되었다 [16,17]. 그 외에도 최 근 사이모신 베타 4는 integrin-linked kinase와 결합하여 survival kinase Akt의 인산화(phosphorylation)를 증가시켜 심근 세포의 이동과 생존을 증가시킨다는 보고가 있어 여러 세포의 이동 및 생리작용에 사이모신 베타 4가 중요한 역할을 담당하 고 있음이 밝혀졌다 [1].…”