Sodium Butyrate as Key Regulator of Mitochondrial Function and Barrier Integrity of Human Glomerular Endothelial Cells
The gut microbiota has emerged as an important modulator of cardiovascular and renal homeostasis. The composition of gut microbiota in patients suffering from chronic kidney disease (CKD) is altered, where a lower number of bacteria producing short chain fatty acids (SCFAs) is observed. It is known...
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MDPI AG
2023-08-01
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| Series: | International Journal of Molecular Sciences |
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| author | Maria Novella Nicese Roel Bijkerk Anton Jan Van Zonneveld Bernard M. Van den Berg Joris I. Rotmans |
| author_facet | Maria Novella Nicese Roel Bijkerk Anton Jan Van Zonneveld Bernard M. Van den Berg Joris I. Rotmans |
| author_sort | Maria Novella Nicese |
| collection | DOAJ |
| description | The gut microbiota has emerged as an important modulator of cardiovascular and renal homeostasis. The composition of gut microbiota in patients suffering from chronic kidney disease (CKD) is altered, where a lower number of bacteria producing short chain fatty acids (SCFAs) is observed. It is known that SCFAs, such as butyrate and acetate, have protective effects against cardiovascular diseases and CKD but their mechanisms of action remain largely unexplored. In the present study, we investigated the effect of butyrate and acetate on glomerular endothelial cells. Human glomerular microvascular endothelial cells (hgMVECs) were cultured and exposed to butyrate and acetate and their effects on cellular proliferation, mitochondrial mass and metabolism, as well as monolayer integrity were studied. While acetate did not show any effects on hgMVECs, our results revealed that butyrate reduces the proliferation of hgMVECs, strengthens the endothelial barrier through increased expression of VE-cadherin and Claudin-5 and promotes mitochondrial biogenesis. Moreover, butyrate reduces the increase in oxygen consumption induced by lipopolysaccharides (LPS)<i>,</i> revealing a protective effect of butyrate against the detrimental effects of LPS. Taken together, our data show that butyrate is a key player in endothelial integrity and metabolic homeostasis. |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T23:23:00Z |
| publishDate | 2023-08-01 |
| publisher | MDPI AG |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-dcfbf0f4e8304ffb95565ad99d1e3f102023-11-19T08:12:25ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-08-0124171309010.3390/ijms241713090Sodium Butyrate as Key Regulator of Mitochondrial Function and Barrier Integrity of Human Glomerular Endothelial CellsMaria Novella Nicese0Roel Bijkerk1Anton Jan Van Zonneveld2Bernard M. Van den Berg3Joris I. Rotmans4Department of Internal Medicine, Division of Nephrology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The NetherlandsDepartment of Internal Medicine, Division of Nephrology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The NetherlandsDepartment of Internal Medicine, Division of Nephrology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The NetherlandsDepartment of Internal Medicine, Division of Nephrology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The NetherlandsDepartment of Internal Medicine, Division of Nephrology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The NetherlandsThe gut microbiota has emerged as an important modulator of cardiovascular and renal homeostasis. The composition of gut microbiota in patients suffering from chronic kidney disease (CKD) is altered, where a lower number of bacteria producing short chain fatty acids (SCFAs) is observed. It is known that SCFAs, such as butyrate and acetate, have protective effects against cardiovascular diseases and CKD but their mechanisms of action remain largely unexplored. In the present study, we investigated the effect of butyrate and acetate on glomerular endothelial cells. Human glomerular microvascular endothelial cells (hgMVECs) were cultured and exposed to butyrate and acetate and their effects on cellular proliferation, mitochondrial mass and metabolism, as well as monolayer integrity were studied. While acetate did not show any effects on hgMVECs, our results revealed that butyrate reduces the proliferation of hgMVECs, strengthens the endothelial barrier through increased expression of VE-cadherin and Claudin-5 and promotes mitochondrial biogenesis. Moreover, butyrate reduces the increase in oxygen consumption induced by lipopolysaccharides (LPS)<i>,</i> revealing a protective effect of butyrate against the detrimental effects of LPS. Taken together, our data show that butyrate is a key player in endothelial integrity and metabolic homeostasis.https://www.mdpi.com/1422-0067/24/17/13090glomerular endothelial cellsshort chain fatty acidsbutyrateproliferationendothelial barriermitochondria |
| spellingShingle | Maria Novella Nicese Roel Bijkerk Anton Jan Van Zonneveld Bernard M. Van den Berg Joris I. Rotmans Sodium Butyrate as Key Regulator of Mitochondrial Function and Barrier Integrity of Human Glomerular Endothelial Cells International Journal of Molecular Sciences glomerular endothelial cells short chain fatty acids butyrate proliferation endothelial barrier mitochondria |
| title | Sodium Butyrate as Key Regulator of Mitochondrial Function and Barrier Integrity of Human Glomerular Endothelial Cells |
| title_full | Sodium Butyrate as Key Regulator of Mitochondrial Function and Barrier Integrity of Human Glomerular Endothelial Cells |
| title_fullStr | Sodium Butyrate as Key Regulator of Mitochondrial Function and Barrier Integrity of Human Glomerular Endothelial Cells |
| title_full_unstemmed | Sodium Butyrate as Key Regulator of Mitochondrial Function and Barrier Integrity of Human Glomerular Endothelial Cells |
| title_short | Sodium Butyrate as Key Regulator of Mitochondrial Function and Barrier Integrity of Human Glomerular Endothelial Cells |
| title_sort | sodium butyrate as key regulator of mitochondrial function and barrier integrity of human glomerular endothelial cells |
| topic | glomerular endothelial cells short chain fatty acids butyrate proliferation endothelial barrier mitochondria |
| url | https://www.mdpi.com/1422-0067/24/17/13090 |
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