Bisphenol A impaired cell adhesion by altering the expression of adhesion and cytoskeleton proteins on human podocytes

Sci Rep. 2020 Oct 6;10(1):16638. doi: 10.1038/s41598-020-73636-6.

Abstract

Bisphenol A (BPA), a chemical -xenoestrogen- used in food containers is present in the urine of almost the entire population. Recently, several extensive population studies have proven a significant association between urinary excretion of BPA and albuminuria. The alteration of glomerular podocytes or "podocytopathy" is a common event in chronic albuminuric conditions. Since many podocytes recovered from patients' urine are viable, we hypothesized that BPA could impair podocyte adhesion capabilities. Using an in vitro adhesion assay, we observed that BPA impaired podocyte adhesion, an effect that was abrogated by Tamoxifen (an estrogen receptor blocker). Genomic and proteomic analyses revealed that BPA affected the expression of several podocyte cytoskeleton and adhesion proteins. Western blot and immunocytochemistry confirmed the alteration in the protein expression of tubulin, vimentin, podocin, cofilin-1, vinculin, E-cadherin, nephrin, VCAM-1, tenascin-C, and β-catenin. Moreover, we also found that BPA, while decreased podocyte nitric oxide production, it lead to overproduction of ion superoxide. In conclusion, our data show that BPA induced a novel type of podocytopathy characterizes by an impairment of podocyte adhesion, by altering the expression of adhesion and cytoskeleton proteins. Moreover, BPA diminished production of podocyte nitric oxide and induced the overproduction of oxygen-free metabolites. These data provide a mechanism by which BPA could participate in the pathogenesis and progression of renal diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzhydryl Compounds / adverse effects*
  • Cell Adhesion / drug effects*
  • Cell Adhesion / genetics*
  • Cells, Cultured
  • Cytoskeletal Proteins / metabolism
  • Estrogen Antagonists / pharmacology
  • Gene Expression / drug effects
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Kidney Diseases / etiology*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Nitric Oxide / metabolism
  • Phenols / adverse effects*
  • Podocytes / metabolism*
  • Podocytes / physiology*
  • Superoxides / metabolism
  • Tamoxifen / pharmacology
  • Tubulin / genetics
  • Tubulin / metabolism
  • Vascular Cell Adhesion Molecule-1 / genetics
  • Vascular Cell Adhesion Molecule-1 / metabolism
  • Vimentin / genetics
  • Vimentin / metabolism

Substances

  • Benzhydryl Compounds
  • Cytoskeletal Proteins
  • Estrogen Antagonists
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • NPHS2 protein
  • Phenols
  • Tubulin
  • Vascular Cell Adhesion Molecule-1
  • Vimentin
  • Tamoxifen
  • Superoxides
  • Nitric Oxide
  • bisphenol A