HMGCS2通过调节PPARγ参与溃疡性结肠炎的发生发展

HMGCS2 Is Involved in the Development of Ulcerative Colitis by Regulating PPARγ

摘要: 目的：探讨3-羟基-3甲基戊二酰辅酶A合酶2 (HMGCS2)通过调节过氧化物酶体增殖物激活受体γ (PPARγ)对溃疡性结肠炎(UC)发生发展的影响。方法：免疫组织化学染色检测HMGCS2蛋白在正常和UC肠道组织的表达。体外培养Caco2和HT29细胞，构建HMGCS2敲低慢病毒载体，分别转染两株细胞后得到sh-NC组、sh-HMGCS2-1组、sh-HMGCS2-2组和sh-HMGCS2-3组。通过Western Blot检测各组细胞过氧化物酶体增殖体激活受体γ (PPARγ)、信号转导和转录激活因子1 (STAT1)、信号转导和转录激活因子3 (STAT3)的蛋白表达。实时荧光定量PCR检测肿瘤坏死因子(TNF-α)、白细胞介素1β (IL-1β)、白细胞介素6 (IL-6) mRNA的表达。结果：与正常肠道组织相比，UC肠道组织中HMGCS2表达水平显著降低(P < 0.05)。与sh-NC相比，sh-HMGCS2组中炎症细胞因子IL-1β、IL-6和TNF-α的mRNA表达水平明显升高(P < 0.05)；PPARγ蛋白表达水平降低(P < 0.05)；STAT1、STAT3蛋白表达水平无统计学差异(P > 0.05)。结论：HMGCS2可能通过调控PPARγ减弱肠上皮细胞炎症反应，参与UC的发生发展。

Abstract: Objective: To investigate the effect of 3-hydroxy-3-methylglutaryl-CoA synthetase 2 (HMGCS2) on the progression of ulcerative colitis (UC) by regulating peroxisome proliferator-activated receptor γ (PPARγ). Methods: The expression of HMGCS2 protein in normal and UC intestinal tissues was detected by immunohistochemical staining. Caco2 and HT29 cells were cultured, and HMGCS2 knockdown lentiviral vectors were constructed to obtain sh-NC group, sh-HMGCS2-1 group, sh-HMGCS2-2 group, and sh-HMGCS2-3 group of the two strains of cells respectively. Western Blot was used to detect the protein expression of PPARγ, signal transducer and activator of transcription 1 (STAT1) and signal transducer and activator of transcription 3 (STAT3) in each group. The mRNA expressions of tumor necrosis factor (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) were detected by real-time fluorescence quantitative PCR. Results: Compared with normal intestinal tissues, the expression level of HMGCS2 in UC intestinal tissues was significantly reduced (P < 0.05). Compared with sh-NC, the mRNA expression levels of inflammatory cytokines IL-1β, IL-6 and TNF-α were significantly higher in the sh-HMGCS2 groups (P < 0.05); the expression level of PPARγ protein was reduced (P < 0.05), while the differences in the expression levels of STAT1 and STAT3 proteins were not statistically significant (P > 0.05). Conclusion: HMGCS2 may attenuate the inflammatory response of intestinal epithelial cells by regulating PPARγ, and participate in the occurrence and development of UC.