Expression And Significance Of Histone Deacetylase1,8in Alveolar Epithelial Type Ⅱ Cells Mesenchymal Transition

Background and Objective: As life expectancy increases and the application oftreatment to cancer chemotherapy in recent years, the incidence of pulmonary fibrosisincreased year by year. The traditional clinical therapy of inhibiting fibrosis progressalthough have a certain effect, but also have the side effects, thus, the application islimited. As other organ fibrosis, pulmonary fibrosis (PF) relates to the jointparticipation of the cells, cytokines, EMT, etc., wherein the Epithelial-MesenchymalTransition (EMT) participate in the regulation of organ fibrosis and otherphysiological and pathological processes, while histone deacetylase (HDACs) alsoplays an important role in these processes. HDACs and Histone acetyltransferase(HAT) are families of nuclear enzymes that modify the expression of inflammatorygenes by regulating chromatin structure. If the balance between the two enzymes isdestroyed, the gene transcription will lead to disorders and changes in signaltransduction, thereby causing gene abnormal expression of this anomaly plays animportant role in the occurrence and development of fibrosis and cancer. The HDACsis divided into four categories, HDAC1,8belong to the class I HDAC. Recent studiessuggest that HDAC1play an important role in the process of liver cells transforminggrowth factor-beta1(TGF-β1)-induced EMT, histone deacetylase inhibitors (HDACi)-Trichostatin A (TSA) can effectively inhibit the class Ⅰ and Ⅱ HDACs, and preventthe fibrosis in chronic liver injury induced by carbon tetrachloride, it can also inhibitthe renal tubular epithelial cell EMT and reduce skin fibrosis after radiotherapy, butHDACs involved in alveolar epithelial cells EMT process is not clear. Thus, weobserve the expression of histone deacetylase1,8on the TGF-β1induced type Ⅱalveolar epithelial cells to mesenchymal transition (EMT) process of RLE-6TN cells,and investigate the effect of histone deacetylase inhibitor Trichostatin A (TSA) on TGF-β1-induced typeⅡalveolar epithelial cells EMT.Methods: RLE-6TN cell lines were cultured and treated with TGF-β1, and collectedcells at different time points. The expression of markers of the epithelial cells(E-cadherin)，mesenchymal cells (α-SMA)，HDAC1and HDAC8were assayed byWestern Blot. The expression of mRNA of E-cad, α-SMA, HDAC1and HDAC8wereassayed by Real-time RT-PCR. On the other hand, we added TGF-β1to the cells afterpretreatment for6hours with TSA and repeat the above assay.Results: Compared with the control group, with the treatment of TGF-β1, theexpression of E-cad protein was downregulated; α-SMA, HDAC1and HDAC8protein was upregulated. E-cad mRNA was downregulated; both the mRNA ofα-SMA and HDAC8were upregulated at12h, and were downregulated at6h,24h;HDAC1mRNA at6h were downregulated,24h was upregulated. Compared withTGF-β1group, after pretreated with TSA, the expression of E-cad protein wasupregulated; α-SMA, HDAC1and HDAC8protein was downregulated. E-cad mRNAwas upregulated; α-SMA mRNA at6h,12h was upregulated,24h was downregulated;HDAC1mRNA was downregulated; HDAC8mRNA was upregulated.Conclusion:1. HDAC1involved in the process of TGF-β1induced RLE-6TN cellsEMT；2. It is possible that using TSA inhibited RLE-6TN cells to receive α-SMAphenotype, loss of E-cad phenotype, which partially reversed the EMT of RLE-6TNinduced by TGF-β1in vitro.