Molecular targets for treatment of kidney fibrosis

J Mol Med (Berl). 2013 May;91(5):549-59. doi: 10.1007/s00109-012-0983-z. Epub 2012 Nov 22.

Abstract

Renal fibrosis is the culmination of processes driven by signaling pathways involving transforming growth factor-β family of cytokines, connective-tissue growth factor, nuclear factor κB, Wnt/β-catenin, Notch, and other growth factors. Many studies in experimental animal models have directly targeted these pathways and demonstrated efficacy in mitigating renal fibrosis. However, only a small fraction of these approaches have been attempted in human and even fewer have been successfully translated to clinical use for patient with kidney diseases. Drugs with proven efficacy for treatment of kidney diseases and tissue fibrosis exert some of their effects by interfering with components of these pathways. This review considers key molecular mediators of renal fibrosis and their potential as targets for treatment of renal fibrosis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Animals
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Humanized
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Connective Tissue Growth Factor / genetics
  • Connective Tissue Growth Factor / metabolism
  • Fibrosis
  • Gene Expression Regulation
  • Humans
  • Kidney / drug effects*
  • Kidney / metabolism
  • Kidney / pathology
  • Molecular Targeted Therapy
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • Protective Agents / therapeutic use*
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism
  • Pyridones / therapeutic use*
  • Signal Transduction / drug effects*
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / metabolism
  • beta Catenin / genetics
  • beta Catenin / metabolism
  • ortho-Aminobenzoates / therapeutic use*

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • CCN2 protein, human
  • CTNNB1 protein, human
  • Carrier Proteins
  • NF-kappa B
  • Protective Agents
  • Pyridones
  • Transforming Growth Factor beta
  • beta Catenin
  • ortho-Aminobenzoates
  • Connective Tissue Growth Factor
  • pirfenidone
  • HIPK2 protein, human
  • Protein Serine-Threonine Kinases
  • tranilast
  • pamrevlumab