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Macrophage migration inhibitory factor regulates integrin-β1 and cyclin D1 expression via ERK pathway in podocytes

Chien-An Chen1, Jer-Ming Chang2, Yu-Lin Yang3

  • 1Department of Nephrology, Tainan Sinlau Hospital, Tainan, 701, Taiwan; Department of Health Care Administration, Chang Jung Christian University, Tainan, 711, Taiwan.

Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie
|January 28, 2020
PubMed
Abstract

Insights

Macrophage migration inhibitory factor (MIF) increases integrin-β1 and cyclin D1 expression in podocytes via the ERK pathway. This up-regulation enhances podocyte adhesion, contributing to proliferative glomerulonephritis.

Area of Science:

  • Nephrology
  • Molecular Biology
  • Cell Biology

Background:

  • Macrophage migration inhibitory factor (MIF) is elevated in proliferative glomerulonephritis.
  • MIF signaling involves its receptor (CD74) and MAP kinases (ERK, p38).
  • Integrins and cyclin D1 are key regulators of cell proliferation, differentiation, and adhesion.

Purpose of the Study:

  • To investigate if MIF regulates integrin-β1 and cyclin D1 expression in podocytes.
  • To determine the role of MIF in podocyte cell adhesion.
  • To elucidate the signaling pathway involved in MIF-induced changes in podocytes.

Main Methods:

  • Real-time PCR and Western blotting assessed integrin-β1 and cyclin D1 mRNA/protein expression under MIF stimulation.
  • MIF receptor (CD74) and MAP kinase activation (ERK, p38) were examined.
  • Cell adhesion assays were performed with MIF treatment and/or anti-integrin-β1 antibody.

Main Results:

  • MIF treatment dose-dependently increased integrin-β1 protein levels.
  • MIF elevated integrin-β1 and cyclin D1 mRNA levels, mediated by the ERK pathway.
  • MIF-induced podocyte adhesion was reduced by anti-integrin-β1 antibody.

Conclusions:

  • MIF up-regulates integrin-β1 and cyclin D1 expression in podocytes through the ERK pathway.
  • Increased integrin-β1 expression by MIF enhances podocyte adhesion.
  • These findings clarify MIF's role in proliferative glomerulonephritis pathogenesis.
Keywords:
Integrin β1Macrophage migration inhibitory factorPodocytes

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