Reference - Detail
| RRC ID | 68155 |
|---|---|
| Author | Xu W, Watanabe K, Mizukami Y, Yamamoto Y, Suzuki T. |
| Title | Hydrogen sulfide suppresses the proliferation of intestinal epithelial cells through cell cycle arrest. |
| Journal | Arch Biochem Biophys |
| Abstract |
The pathogenesis of chronic kidney disease (CKD) is closely related to the changes in the intestinal microbiota and integrity. Our previous studies have shown the accumulation of hydrogen sulfide (H2S)-producing bacterial family, Desulfovibrionacea, in the colon of a murine model of CKD, suggesting that the increased H2S contributes to the impaired intestinal integrity in CKD. Here, we investigated the anti-proliferative effect of H2S in the intestinal epithelial cells. A slow- H2S releasing molecule GYY4137 ((p-methoxyphenyl)morpholino-phosphinodithioic acid) reduced the proliferation of Caco-2 and IEC-6 cells. Flow cytometric analysis demonstrated that GYY4137 accumulated Caco-2 cells in the S phase fraction, suggesting that H2S arrested the cell cycle at G2 and/or M phases. The RNA sequencing analysis demonstrated that GYY4137 modulated the mRNA expression of the genes involved in the G2/M and the spindle assembly checkpoints; increased mRNA levels of Cdkn1a, Gadd45a, and Sfn and decreased mRNA levels of Cdc20, Pttg1, and Ccnb1 were observed. These alterations were confirmed by quantitative reverse transcription-polymerase chain reaction and Western blot analyses. Besides, studies exploring the MEK inhibitor indicated that MEK activation is involved in the GYY4137-mediated increase in the Sfn expression. Altogether, our data showed that H2S reduced the proliferation of intestinal epithelial cells through transcriptional regulation in G2/M and the spindle assembly checkpoints. This may be one of the underlying mechanisms for the observed impaired intestinal integrity in CKD. |
| Volume | 712 |
| Pages | 109044 |
| Published | 2021-11-15 |
| DOI | 10.1016/j.abb.2021.109044 |
| PII | S0003-9861(21)00293-9 |
| PMID | 34597656 |
| MeSH | Animals Cell Line, Tumor Cell Proliferation / drug effects* Epithelial Cells / drug effects* G2 Phase Cell Cycle Checkpoints / drug effects* Gene Expression Regulation / drug effects Humans Hydrogen Sulfide / pharmacology* Intestines / cytology MAP Kinase Signaling System / drug effects Morpholines / pharmacology Organothiophosphorus Compounds / pharmacology Rats |
| IF | 3.391 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 3 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | IEC 6(RCB0993) |