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

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.

Critical Analysis of Human Exposure to Bisphenol A and Its Novel Implications on Renal, Cardiovascular and Hypertensive Diseases

“…* or @ means p-value < 0,05; ** or @@ means p < 0,01; *** or @@@ means p < 0,001; **** or @@@@ means p < 0,0001. Figure made with our own results published in the Journal of Cellular Physiology [22], FASEB Journal [27] and Scientific Reports [24].…”

“…By using transcriptomics, proteomics, western-blot, and immunocytochemistry, it was possible to determine that BPA at low doses promotes a reduction in the expression of numerous structural or adhesion proteins, such as tubulin, vimentin, podocin, cofilin-1, vinculin, E-cadherin, nephrin, and VCAM-1, as well as an increase in the expression of proteins that negatively participate in adhesion mechanisms, such as Tenascin-C [24].…”

Bisphenol a Exposure and Kidney Diseases: Systematic Review, Meta-Analysis, and NHANES 03–16 Study

“…In this sense, previous studies developed by our team determined that mouse podocytes (cells that are part of the glomerular filtration barrier) treated with BPA (10 and 100 nM) underwent apoptosis followed by podocytopenia, albuminuria [12], and hypertension. Interestingly, when treating cultured human podocytes at the same doses of BPA, we observed a podocytopathy characterized by impaired cell adhesion due to alteration in the expression of the podocyte's adhesion and structural proteins [13]. Furthermore, epidemiological studies in humans have found interesting relationships between BPA concentration in blood or urine and the risk of developing kidney disease [21][22][23][24].…”

“…Currently, the European Food Safety Authority (EFSA) has delimited a tolerable daily intake (TDI) up to 4 µg/kg body weight/day, based on studies by Tyl et al (2008) on the ability of BPA to affect the kidneys [6,7]. However, only a small percentage of publications study the BPA-kidney paradigm [8][9][10][11][12][13], compared to other organs and systems such as the reproductive or endocrine systems [14][15][16][17][18][19][20]. In this sense, previous studies developed by our team determined that mouse podocytes (cells that are part of the glomerular filtration barrier) treated with BPA (10 and 100 nM) underwent apoptosis followed by podocytopenia, albuminuria [12], and hypertension.…”

Bisphenol A Induces Accelerated Cell Aging in Murine Endothelium

“…However, in the last two decades, evidence correlates BPA with other types of pathologies such as diabetes, obesity, and even cognitive and behavioral disorders [14][15][16][17]. Our group has recently found new evidence that positions BPA as a possible environmental factor promoting nephro-vascular pathologies [18][19][20][21]. Currently, few studies explore the cardiovascular system, but there are population studies that correlate high concentrations of urinary BPA with an increased risk of developing arterial hypertension [22,23].…”