Novel therapeutic targets for the treatment of tubulointerstitial fibrosis

Jai Prakash, Klaas Poelstra, Harry van Goor, Frits Moolenaar, Dirk K.F. Meijer, Robbert J. Kok*

*Corresponding author for this work

Research output: Contribution to journalReview articleAcademicpeer-review

4 Citations (Scopus)

Abstract

Approximatety 80% of the kidney is composed of tubular cells which secret and reabsorb substances to and from the urine. Activated tubular cells play a pivotal role in the etiology of renal fibrosis. During renal injury, these activated tubular cells participate in the initiation of fibrogenic processes which eventually may lead to tubulointerstitial fibrosis and end stage renal disease (ESRD). Current therapies such as angiotensin converting enzyme inhibitors, angiotensin II receptor type-1 antagonists and statins do not suffice for the treatment of renal fibrosis. However, in recent years, better understanding of disease mechanisms led to the development of new drug entities that intervene in the signal transduction pathways involved in the disease pathogenesis. This review discusses possible new drugs directed to intracellular signal transduction pathways such as mitogen-activated protein kinases (p38, ERK and JNK), growth factors receptor tyrosine kinases (TGF-β and PDGF), Rho kinase, and nuclear transcription factors that are activated during disease. In addition to kinase inhibitors, novel approaches such as renal-selective drug targeting, recombinant protein antifibrotic agents and gene silencing concepts are discussed.

Original languageEnglish
Pages (from-to)97-111
Number of pages15
JournalCurrent Signal Transduction Therapy
Volume3
Issue number2
DOIs
Publication statusPublished - 1 May 2008
Externally publishedYes

Keywords

  • Drug targeting
  • Inflammation
  • Kidney
  • Kinase inhibitors
  • Signal transduction
  • Tubulointerstitial fibrosis

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    Prakash, J., Poelstra, K., van Goor, H., Moolenaar, F., Meijer, D. K. F., & Kok, R. J. (2008). Novel therapeutic targets for the treatment of tubulointerstitial fibrosis. Current Signal Transduction Therapy, 3(2), 97-111. https://doi.org/10.2174/157436208784223161