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Dissecting the Involvement of Ras GTPases in Kidney Fibrosis

José M Muñoz-Félix1,2, Carlos Martínez-Salgado2,3

  • 1Department of Biochemistry and Molecular Biology, University of Salamanca, 37007 Salamanca, Spain.

Genes
|June 2, 2021
PubMed

Insights

Small Ras GTPases and their effectors play a key role in kidney fibrosis development by regulating myofibroblast activation and extracellular matrix accumulation. Targeting the Ras pathway offers potential therapeutic strategies for renal fibrosis.

Area of Science:

  • Nephrology
  • Molecular Biology
  • Cellular Biology

Background:

  • Transforming growth factor-β1 (TGF-β1) signaling is a well-studied regulator of renal fibrosis.
  • Emerging evidence highlights the involvement of other pathways, including small Ras GTPases, in renal fibrosis.
  • Ras GTPases are implicated in key fibrotic processes like myofibroblast activation and extracellular matrix (ECM) deposition.

Purpose of the Study:

  • To review current in vitro and in vivo knowledge on the role of Ras GTPases in renal fibrosis.
  • To explore the interplay between TGF-β1 and Ras signaling in kidney fibrosis.
  • To discuss therapeutic strategies targeting the Ras pathway for renal fibrosis intervention.

Main Methods:

  • Literature review of in vitro and in vivo studies.
  • Analysis of signaling pathways involved in renal fibrosis.
  • Examination of Ras effectors (Erk, Akt) in fibrotic processes.

Main Results:

  • Ras GTPases regulate myofibroblast activation and proliferation.
  • Ras signaling influences extracellular matrix (ECM) synthesis and accumulation.
  • Ras pathway components are involved in tubular epithelial cell apoptosis and survival.

Conclusions:

  • Ras GTPases are critical regulators of cellular mechanisms in renal fibrosis.
  • The interaction between TGF-β1 and Ras pathways is significant in fibrosis development.
  • Targeting the Ras pathway presents a promising therapeutic avenue for renal fibrosis.
Keywords:
AktMAP kinasesRasextracellular matrixfibroblastskidney fibrosis

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