ASN's Mission

ASN leads the fight to prevent, treat, and cure kidney diseases throughout the world by educating health professionals and scientists, advancing research and innovation, communicating new knowledge, and advocating for the highest quality care for patients.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on Twitter

Kidney Week

Abstract: TH-PO790

Gut Microbial Metabolite Butyrate Protects Podocytes from Damage Through Epigenetic-Mediated Mechanisms

Session Information

Category: Glomerular Diseases

  • 1201 Glomerular Diseases: Fibrosis and Extracellular Matrix

Authors

  • Felizardo, Raphael F., Federal University of São Paulo, São Paulo, São Paulo, Brazil
  • Almeida, Danilo Candido, Federal University of São Paulo, São Paulo, São Paulo, Brazil
  • Andrade-Oliveira, Vinicius, University of São Paulo, São Paulo, São Paulo, Brazil
  • Pereira, Rafael Luiz, Universidade Federal do Paraná, Curitiba, Brazil
  • Watanabe, Ingrid Kazue Mizuno, Federal University of São Paulo, São Paulo, São Paulo, Brazil
  • Camara, Niels OS, Federal University of São Paulo, São Paulo, São Paulo, Brazil
Background

Chronic Kidney Disease (CKD) is characterized by gradual impairment of renal function over a period of months or years leading to permanent kidney failure. The damages or loss of podocytes, specialized cells involved on filtration process, stand as one of the most important causes that lead to a CKD. The literature comprises a large number of experimental attempts that focus on mitigating the damage to the podocytes. In recent years, many studies point to the gut microbiota as a modulator of intestinal and extraintestinal diseases through the generation of short chain fatty acids (SCFA). It is already known that chronic kidney patients have an imbalanced gut microbiota and lower production of SCFA. Thus, we have explored the protective role of butyrate, an AGCC able to regulate epigenetic processes during the progression of experimental glomerulopathy induced by doxorubicin.

Methods

Wild type mice were induced to develop glomerulopathy by a single dose of doxorubicin and treated with butyrate.

Results

Wild type mice treated with butyrate showed improvement of renal function, associated to a preserved podocyte layer in the glomerular basement membrane and reduction of pro-inflammatory and pro-fibrotic markers in the kidneys. Particularly, butyrate modulated the activity of enzymes involved on epigenetic modifications in the kidneys and changed the levels of histone markers (H3K9Ac, H3K4me3 and H3K9me3) in the promoter region of the genes encoding synaptopodin, podocin and NEPH-1 in podocytes. Concomitantly, treatment with butyrate was associated with the regulations of small GTPases activity Rac1 and Cdc42 and maintenance of the organization of actin filaments in the podocytes grown in vitro.

Conclusion

Our results demonstrate that butyrate exerts relevant effects on podocyte homeostasis during experimental nephropathy through epigenetic mediated mechanisms. FAPESP grant numbers 2012/15205-4, 2012/02270-2, 2017/06222-06 and 2017/05264-7.