Previously we demonstrated that progesterone at physiologic levels dose dependently inhibited cell proliferation in cultured rat aortic smooth muscle cells (RASMCs). However, the molecular mechanism underlying of progesterone-induced antiproliferation was not clear. Here we demonstrated that progesterone induced a reduction of the [(3)H]thymidine incorporation into RASMCs during the S-phase of the cell cycle. Western blotting analysis revealed that the protein levels of cyclin A, cyclin E, and cyclin-dependent-kinase (CDK) 2 but not cyclin D1 and CDK4 decreased after progesterone treatment, but those of CDK-inhibitory proteins, p21 and p27, increased. Immunoprecipitation showed that the formations of the CDK2-p21 and CDK2-p27 complex were increased and the assayable CDK2 kinase activity was decreased in the progesterone-treated RASMCs. In contrast, the formations of the CDK4-p21 and CDK4-p27 complex and the assayable CDK4 kinase activity were not changed significantly by progesterone treatment. Pretreatment of RASMCs with a p21 or p27 antisense oligonucleotide reduced the progesterone-induced inhibition of [(3)H]thymidine incorporation into RASMCs. In conclusion, these data suggest that progesterone inhibits RASMCs proliferation by increasing the levels of p21 and p27 protein, which in turn inhibit CDK2 kinase activity, and finally interrupt the cell cycle.
A growing body of study have documented the association of gut dysbiosis or fecal metabolites with chronic kidney disease (CKD). However, it is not clear whether the phenomenon simply reflects the microenvironment changes correlated with the CKD severity or contributes to the progression of CKD. In this study, we identified the gut microbiota and metabolite in feces samples correlated with CKD severity using the Nanopore long-read sequencing platform and UPLC-coupled MS/MS approach. A cross-sectional cohort study was performed from 1 June 2020 to 31 December 2020. One hundred and fifty-six clinical participants, including 60 healthy enrollees and 96 Stage 1–5 CKD patients, were enrolled in this study. The ROC curve generated with the relative abundance of Klebsiella pneumonia or S-Adenosylhomocysteine showed a gradual increase with the CKD severity. Our results further revealed the positive correlation of increased K. pneumonia and S-Adenosylhomocysteine in gut environment, which may be of etiological importance to the deterioration of a CKD patient. In that sense, the microbiota or metabolite changes constitute potential candidates for evaluating the progression of CKD.
Highlights
Differential splicing profiles of
MBNL1
and
Acin1
gene is noted in CRC tissues or cells.
Autoregulated exclusion of
MBNL1
exons is altered with upregulated SRSF3
MBNL1 isoform differentially modulates CRC-related AS events.
SRSF3 and MBNL1 exerts opposite impact on expression of the Acin1 isoform.
Acin1 isoform exhibits distinct influence on DNA fragmentation in CRC cells.
SRSF3-MBNL11-Acin1 constitutes an emerging circuit involved in apoptosis of CRC cells.
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