Long-term Y-27632 treatment promotes senescence of primary human dermal fibroblasts by increasing IGFBP-5
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PROVIDER: PRJNA560681 | ENA |
REPOSITORIES: ENA
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Project description:Purpose: Y-27632, a well-characterized Rho-associated kinase (ROCK) inhibitor, has been shown to play an important role in regulation of cell growth in multiple types of cells, the regulation appeared to be cell specific. To further understand its molecular mechanisms, we performed RNA-seq analysis of HDF at 12 hours and 48 hours after Y-27632 treatment. Methods: Total RNAs were isolated from dermal cells with/without Y-27632 treatment for 12 hours or 48 hours respectively. Then mRNAs were purified from above total RNA using poly-T oligo-attached magnetic beads. After sequencing libraries were prepared using NEBNext® UltraTM RNA Library Prep Kit for Illumina® (NEB, USA), the library preparations were sequenced on an Illumina Hiseq platform and 125 bp/150 bp paired-end reads were generated. Results: We sequenced 12 of 229 differential expressed genes 48 hours after Y-27632 treatment and found genes which by GO analysis are negative regulators of cell growth ). Of these 12 genes, the expression level of 4 genes, IGFBP1, IGFBP-5, HNF4A and NKD1, changed significantly at both 12 hours and 48 hours of Y-27632 treatment. This results, validated by RT-qPCR analysis showed that the expression of IGFBP-5 (Insulin Growth Factor Binding Protein 5) increased by 1.5 fold after 12 hours of treatment, and increased more than 10-fold after 48 hours. Expression of the other 3 genes didn’t change significantly after Y-27632 treatment Conclusions:RNA-seq analysis of gene expression profile in HDFs collected from 12 hours and 48 hours treatment of Y-27632. From these analyses we found the IGFBP-5, a negative regulation of cell proliferation, whose expression increased with the duration of Y-27632 treatment (7-fold increase after the first 24 hours
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Project description:Histone deacetylases (HDACs) are known to be a class of enzymes that remove acetyl groups from lysine chains on histones or other proteins, and play a crucial role in epigenetic regulation and aging process. Previous studies have identified that HDAC4 is down-regulated in aged and UV-irradiated skin in vivo. Therefore, HDAC4 may be an important role in skin aging process. However, the role of HDAC4 in skin aging is rarely known. In this study, we conducted the integrative transcriptome analysis of overexpression and knockdown of HDAC4, and UV- or H2O2-induced senescence in human dermal fibroblast and identified candidate genes which are regulated by HDAC4. Among these genes, DNA damage-inducible transcript 4 (DDIT4) was significantly regulated by HDAC4. We demonstrated that DDIT4 expression was downregulated during senescence and HDAC4 overexpression prevented senescence-induced decrease of DDIT4. In addition, overexpression of DDIT4 reduced SASP and aged-related genes that could promote aging, suggesting that DDIT4 may prevent senescence. Collectively, our results have shown that HDAC4 may play an important role in preventing skin aging by inducing DDIT4 expression.
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Project description:We investigated the role of AMPK activation in the progression of senescence in HFDPCs. The anti-senescence effects of adenine, a recently identified AMPK activator, were determined in a comparison with AICAR, a pharmacological AMPK activator, in HFDPCs. The results showed that either adenine or AICAR induced phosphorylation of Thr172 of AMPK in HFDPCs. As revealed by microarray analysis, significant changes of gene expression pattern were observed in the high-passage HFDPCs compared with that at lower passage level. A chip study using total RNA recovered from three separate wild-type cultures of Human follicle dermal papilla cells (HFDPCs) and three separate cultures of a triple adenine-treated cells.
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