Thymosin-β4: A key modifier of renal disease

ABSTRACT

Introduction: There is an urgent need for new treatments for chronic kidney disease (CKD). Thymosin-β4 is a peptide that reduces inflammation and fibrosis and has the potential to restore endothelial and epithelial cell injury, biological processes involved in the pathophysiology of CKD. Therefore, thymosin-β4 could be a novel therapeutic direction for CKD.

Areas covered: Here, we review the current evidence on the actions of thymosin-β4 in the kidney in health and disease. Using transgenic mice, two recent studies have demonstrated that endogenous thymosin-β4 is dispensable for healthy kidneys. In contrast, lack of endogenous thymosin-β4 exacerbates mouse models of glomerular disease and angiotensin-II-induced renal injury. Administration of exogenous thymosin-β4, or its metabolite, Ac-SDKP, has shown therapeutic benefits in a range of experimental models of kidney disease.

Expert opinion: The studies conducted so far reveal a protective role for thymosin-β4 in the kidney and have shown promising results for the therapeutic potential of exogenous thymosin-β4 in CKD. Further studies should explore the mechanisms by which thymosin-β4 modulates kidney function in different types of CKD. Ac-SDKP treatment has beneficial effects in many experimental models of kidney disease, thus supporting its potential use as a new treatment strategy.

KEYWORDS:

• Ac-SDKP
• cytoskeleton
• fibrosis
• glomerulus
• inflammation
• kidney disease
• podocyte
• thymosin-β4

Article highlights

• Thymosin-β4 is expressed in the mouse kidney in both health and disease.

• Endogenous thymosin-β4 is dispensable in healthy mouse kidneys.

• In mouse models of immune-mediated and hypertensive renal disease, lack of endogenous thymosin-β4 exacerbates disease progression.

• The protective role of thymosin-β4 is associated with the modulation of podocyte migration, inflammation and fibrosis.

• Treatment with exogenous thymosin-β4 has demonstrated therapeutic benefits in mouse models of interstitial fibrosis and diabetic nephropathy.

• Ac-SDKP treatment is beneficial in a number of experimental models of renal disease including interstitial fibrosis and glomerular disease induced by hypertension, diabetes or inflammation.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose

Additional information

Funding

E. Vasilopoulou is supported by a Kidney Research UK Post-Doctoral Fellowship [PDF8/2015]. D. A. Long’s laboratory is supported by a Medical Research Council New Investigator Award [MR/J003638/1] and project grant [MR/P018629/1], project grants from Diabetes UK [13/0004763, 15/0005283] and Kidney Research UK [RP36/2015], and by the National Institute for Health Research Biomedical Research Centre at Great Ormond Street Hospital for Children NHS Foundation Trust and University College London. This paper has been published as part of a supplement issue covering the proceedings of the Fifth International Symposium on Thymosins in Health and Disease and is funded by SciClone Pharmaceuticals.