Correlation analysis of liver tumor-associated genes with liver regeneration.

AIM: To study at transcriptional level the similarities and differences of the physiological and biochemical activities between liver tumor (LT) and regenerating liver cells. METHODS: LT-associated genes and their expression changes in LT were obtained from databases and scientific articles, and their expression profiles in rat liver regeneration (LR) were detected using Rat Genome 230 2.0 array. Subsequently their expression changes in LT and LR were compared and analyzed. RESULTS: One hundred and twenty one LT-associated genes were found to be LR-associated. Thirty four genes were up-regulated, and 14 genes were down-regulated in both LT and regenerating liver; 20 genes up-regulated in LT were down-regulated in regenerating liver; 21 up-regulated genes and 16 down-regulated genes in LT were up-regulated at some time points and down-regulated at others during LR. CONCLUSION: Results suggested that apoptosis activity suppressed in LT was still active in regenerating liver, and there are lots of similarities and differences between the LT and regenerating liver at the aspects of cell growth, proliferation, differentiation, migration and angiogenesis.

Expression patterns and action analysis of genes associated with hepatitis virus infection during rat liver regeneration.

AIM: To study the action of hepatitis virus infection-associated genes at transcription level during liver regeneration (LR). METHODS: Hepatitis virus infection-associated genes were obtained by collecting the data from databases and retrieving the correlated articles, and their expression changes in the regenerating rat liver were detected with the rat genome 230 2.0 array. RESULTS: Eighty-eight genes were found to be associated with liver regeneration. The number of genes initially and totally expressed during initial LR [0.5-4 h after partial hepatectomy (PH)], transition from G0 to G1 (4-6 h after PH), cell proliferation (6-66 h after PH), cell differentiation and reorganization of structure-function (66-168 h after PH) was 37, 8, 48, 3 and 37, 26, 80, 57, respectively, indicating that the genes were mainly triggered at the early stage of LR (0.5-4 h after PH), and worked at different phases. These genes were classified into 5 types according to their expression similarity, namely 37 up-regulated, 9 predominantly up-regulated, 34 down-regulated, 6 predominantly down-regulated and 2 up/down-regulated genes. Their total up- and down-regulation frequencies were 359 and 149 during LR, indicating that the expression of most genes was enhanced, while the expression of a small number of genes was attenuated during LR. According to time relevance, they were classified into 12 groups (0.5 and 1 h, 2 and 4 h, 6 h, 8 and 12 h, 16 and 96 h, 18 and 24 h, 30 and 42 h, 36 and 48 h, 54 and 60 h, 66 and 72 h, 120 and 144 h, 168 h), demonstrating that the cellular physiological and biochemical activities during LR were fluctuated. According to expression changes of the genes, their expression patterns were classified into 23 types, suggesting that the cellular physiological and biochemical activities during LR were diverse and complicated. CONCLUSION: The anti-virus infection capacity of regenerating liver can be enhanced and 88 genes play an important role in LR.

Estrogen leads to reversible hair cycle retardation through inducing premature catagen and maintaining telogen.

Estrogen dysregulation causes hair disorder. Clinical observations have demonstrated that estrogen raises the telogen/anagen ratio and inhibits hair shaft elongation of female scalp hair follicles. In spite of these clinical insights, the properties of estrogen on hair follicles are poorly dissected. In the present study, we show that estrogen induced apoptosis of precortex cells and caused premature catagen by up-regulation of TGF ß2. Immediately after the premature catagen, the expression of anagen chalone BMP4 increased. The up-regulation of BMP4 may further function to prevent anagen transition and maintain telogen. Interestingly, the hair follicle stem cell niche was not destructed during these drastic structural changes caused by estrogen. Additionally, dermal papilla cells, the estrogen target cells in hair follicles, kept their signature gene expressions as well as their hair inductive potential after estrogen treatment. Retention of the characteristics of both hair follicle stem cells and dermal papilla cells determined the reversibility of the hair cycle suppression. These results indicated that estrogen causes reversible hair cycle retardation by inducing premature catagen and maintaining telogen.

NASA-approved rotary bioreactor enhances proliferation of human epidermal stem cells and supports formation of 3D epidermis-like structure.

The skin is susceptible to different injuries and diseases. One major obstacle in skin tissue engineering is how to develop functional three-dimensional (3D) substitute for damaged skin. Previous studies have proved a 3D dynamic simulated microgravity (SMG) culture system as a "stimulatory" environment for the proliferation and differentiation of stem cells. Here, we employed the NASA-approved rotary bioreactor to investigate the proliferation and differentiation of human epidermal stem cells (hEpSCs). hEpSCs were isolated from children foreskins and enriched by collecting epidermal stem cell colonies. Cytodex-3 micro-carriers and hEpSCs were co-cultured in the rotary bioreactor and 6-well dish for 15 days. The result showed that hEpSCs cultured in rotary bioreactor exhibited enhanced proliferation and viability surpassing those cultured in static conditions. Additionally, immunostaining analysis confirmed higher percentage of ki67 positive cells in rotary bioreactor compared with the static culture. In contrast, comparing with static culture, cells in the rotary bioreactor displayed a low expression of involucrin at day 10. Histological analysis revealed that cells cultured in rotary bioreactor aggregated on the micro-carriers and formed multilayer 3D epidermis structures. In conclusion, our research suggests that NASA-approved rotary bioreactor can support the proliferation of hEpSCs and provide a strategy to form multilayer epidermis structure.

The expression changes of genes associated with protein metabolism, folding, transport, localizati on and assembly during rat liver regeneration.

To study the expression and function of protein metabolism, folding, transport, localization and assembly-associated genes in rat liver regeneration (LR) at transcriptional level, we obtained above genes from databases and scientific articles, detected their expression profiles in rat LR using Rat Genome 230 2.0 array, and determined liver regeneration-associated genes by comparing the partial hepatectomy (PH) group with sham operation (SO) group. Totally 1147 genes were preliminarily confirmed to be LR-associated. The results from the chip detection demonstrated that genes involved in the above biological processes were mostly up-regulated in rat LR; protein metabolism-participating genes were initially expressed mainly at 0.5-1 h and 16-30 h following PH; protein degradation-accelerating genes outnumbered protein accumulation-promoting genes between 0.5-12 h, whereas the latter were more than the former during 16-48 hours; protein synthesis-involved genes were more frequently up-regulated at 16,24,42 and 66 h, especially at 42 h; up-regulation of protein degradation-associated genes dominated almost during the whole period of LR, especially at forepart and prophase; the up-regulated protein folding-associated genes were predominant than down-regulated at 2, 16-24, 42, 66, 72 and 168 h, especially at 66 h; protein transport and localization-associated genes were predominantly up-regulated during the whole period of LR, especially at 66 h; and most of protein complex assembly-associated genes were up-regulated before 96 h, especially at 12 h. it was inferred according to the above analysis that protein synthesis was enhanced at metaphase of LR, and the activities of protein degradation, folding, transport, localization and assembly were vigorous almost during the whole period of LR.