Reduction of PGRN increased fibrosis during skin wound healing in mice.

Progranulin (PGRN) is a multi-functional growth factor known to be involved in regulating of development, cell cycle progression, cell motility, tumorigenesis and angiogenesis. Research has revealed that PGRN is a crucial mediator of skin wound healing. Nonetheless, the role of PGRN in the fibrosis process of cutaneous wound healing has not been identified. In the present study, mice with excisional wounds were treated with si-m-PGRN or physiological saline. We observed the expression of PGRN in intact and post-injury skin by immunohistochemistry. Tissue sections of skin around the wound were performed by hematoxylin & eosin and masson's trichrome staining. After PGRN knockdown by siRNA, the expression of PGRN, collagen I (Col I), small mothers against decapentaplegic homolog 3 (Smad3), phosphorylated Smad3 (P-Smad3), transforming growth factor (TGF)-ß1 and TGF-ß receptor I (TßRI) were detected by real-time reverse transcription polymerase chain reaction (RT-qPCR) or Western blot. PGRN mRNA and protein expressions were increased after insult and remained above that of intact skin through day 20. Down-regulation of PGRN augmented fibrosis area, skin thickness and the expression of Col I. In addition, reduction of PGRN considerably increased the expression of TGF-ß1, TßRI, Smad3 and P-Smad3. These results indicate that PGRN knockdown enhances the fibrosis degree, probably via the TGF-ß/Smad signaling pathway.

Gene expression profile of human esophageal squamous carcinoma cell line TE-1.

Esophageal squamous cell carcinoma (ESCC) is one of the most common and deadly causes of cancer worldwide. However, to date, the mechanisms underlying its pathogenesis remain unclear. The present study investigated the gene expression profile of human esophageal cancer cell line TE-1, a cell model for ESCC, to gain insight to the genetic regulation of this disease. Human esophageal cancer TE-1 cells and normal esophageal HET-1A cells were cultured for isolation of total RNA. Differential expression of RNA transcripts was assessed using the Agilent 4×44 K microarray, combined with real-time PCR (qRT-PCR) for validation. Classification and function of the differential genes were illustrated by bioinformatics processing including hierarchical clustering and gene ontology (GO) analysis. We identified 4,986 transcripts with differential expression (fold-change ≥1.5, P<0.05), including 2,368 up-regulated and 2,618 down-regulated transcripts. GO analysis showed that the dysregulated transcripts were associated with biological process, cellular component, and molecular function. After bioinformatic analysis of significantly regulated signaling pathways, we found these transcripts may target 35 gene pathways, including p53 signaling, glioma, ubiquitin-mediated proteolysis, insulin signaling, cell cycle, inositol phosphate metabolism, mTOR signaling, and MAPK signaling. The differentially expressed transcripts were screened between the esophageal cancer cell line TE-1 and normal esophageal cell line HET-1A, as well as their target gene pathways. Further data mining is related to prevention and treatment of esophageal cancer.

[Nitric oxide mediated TNF-α, IL-1ß gene expression in liver induced by crush injury of rat's soft tissues].

OBJECTIVE: To explore the effect of nitric oxide (NO) on the gene expression of hepatic TNF-α and IL-1ß by crush injury of rat's soft tissues. METHODS: Rats were randomly divided into sham group, crush group, crush+aminoguanidine (AG) group, and crush+L-arginine (L-Arg) group. Activities of ALT and AST as well as NO level in serum were measured. Gene expressions of TNF-α and IL-1ß were detected with RT-PCR. RESULTS: Obvious increase in TNF-α and IL-1ß mRNA expression was detected in the crush group compared with the sham group (P<0.05). After pretreated L-Arg, expressions of TNF-α and IL-1ß mRNA were markedly increased (P<0.05). After pretreated AG, those indices obviously decreased (P<0.05). Activities of ALT and AST enhanced and NO level increased in the crush group compared with the sham group (P<0.05). Pretreatment with L-Arg or AG led to substantial increased or reduced activities of ALT and AST as well as NO levels, respectively. CONCLUSION: Endogenous NO mediated TNF-α, IL-1ß mRNA up expression in liver induced by increased production of NO after crush injury of rat's soft tissues.

Expression of paxillin and FAK mRNA and the related clinical significance in esophageal carcinoma.

The objective of the present study was to investigate the expression of paxillin and focal adhesion kinase (FAK) mRNA in esophageal carcinoma tissues, and their relationship with clinicopathological parameters, as well as to analyze the correlation of paxillin and FAK mRNA levels in esophageal carcinoma. By using reverse transcription polymerase chain reaction (RT-PCR), the mRNA expression levels of paxillin and FAK were detected in 121 samples of esophageal carcinoma, 43 samples of atypical hyperplasia and 56 samples of normal esophageal mucosa. The results showed that the positive rates of paxillin and FAK mRNA expression in esophageal carcinoma were 87.6 and 80.17%, respectively, which were significantly higher (P<0.05) than those in atypical hyperplasia (44.19 and 39.53%) and normal esophageal mucosa (5.36 and 12.5%). Notably, paxillin and FAK mRNA expression levels were significantly correlated with the differentiation degree and depth of invasion of esophageal carcinoma and with lymph node metastasis (P<0.05). In addition, paxillin and FAK mRNA expression levels in esophageal carcinoma were positively correlated (r=0.4804, P=0.000). In conclusion, the combined detection of paxillin and FAK mRNA expression is expected to provide a theoretical basis for the molecular diagnosis of esophageal carcinoma.