A Microbiome-Derived Peptide Induces Apoptosis of Cells from Different Tissues.

Haruko Saiki,Esteban C Gabazza,Taro Yasuma,Hajime Fujimoto,Corina N D’Alessandro-Gabazza,Yuko Okano,Valeria Fridman D’Alessandro,Tatsuki Tsuruga,Tetsu Kobayashi,Masaaki Toda,Keiichi Yamanaka,Ahmed M Abdel-Hamid,Masahiko Sugimoto,Atsuro Takeshita,Kan Katayama,Isaac Cann

doi:10.3390/cells10112885

Haruko Saiki, Esteban C Gabazza + Show 14 more

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https://doi.org/10.3390/cells10112885

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Abstract

Apoptosis is a programmed cell death involved in embryogenesis and tissue homeostasis under physiological conditions. However, abnormalities in the process of apoptosis are implicated in the pathogenesis of various diseases. The human microbiota may release products that induce apoptosis of host cells. We recently identified a novel microbiome-derived peptide called corisin that worsens lung fibrosis by inducing apoptosis of lung epithelial cells. We hypothesized that corisin and a corisin-like peptide might also induce apoptosis of cells from different tissues. We cultured podocytes, renal tubular epithelial cells, keratinocytes, retinal and intestinal cells treated with corisin and evaluated apoptosis by flow cytometry and Western blotting. Although at different grades, flow cytometry analysis and Western blotting showed that corisin and a corisin-like peptide induced apoptosis of podocytes, keratinocytes, tubular epithelial cells, retinal, and intestinal cells. In addition, we found that corisin synergistically enhances the proapoptotic activity of transforming growth factor-β1 on podocytes. In conclusion, these results suggest that corisin and corisin-like peptides may play a role in the pathogenesis of disease in different organs by promoting apoptosis of parenchymal cells.

Highlights

Apoptosis is a programmed cell death with active participation in embryogenic development and maintenance of tissue homeostasis under physiological conditions [1]
This study shows that microbiome-derived peptides induce apoptosis of cells from different tissues and that corisin enhances the proapoptotic activity of TGFβ1 on podocytes synergistically
Corisin is a fragment of bacterial transglycosylase, and its sequence is well conserved among microbes of the genus Staphylococcus [21]

Summary

Introduction

Apoptosis is a programmed cell death with active participation in embryogenic development and maintenance of tissue homeostasis under physiological conditions [1]. It may be extrinsic or intrinsic, depending on the activation pathway. Extrinsic apoptosis is triggered by extracellular stress signals detected by transmembrane death receptors [1]. Intrinsic apoptosis is initiated by the mitochondrion, activated by the withdrawal of growth factors, hypoxia, oxidative stress, and finely regulated by the B-cell lymphoma 2 (Bcl-2). Abnormalities in the process of apoptosis are implicated in the mechanism of several diseases. Recent studies implicated the host microbiome in pathologic apoptosis [17,18,19]

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