title: Role of NLRC5 in progression and reversal of hepatic fibrosis.
abstract: BACKGROUND
  NLRC5, as the largest member of NLRs family, has recently been identified as a critical regulator of immune responses through negatively regulating NF-κB which is associated with the development of hepatic fibrosis. However, the expression and potential roles of NLRC5 in hepatic fibrosis and its reversal are still to be defined.
  
  
  METHODS
  C57BL/6 mice were treatment with carbon tetrachloride (CCl4) induce hepatic fibrosis and its reversal. In vitro, models of hepatic fibrosis and its reversal are established by the treatment with TGF-β and MDI. The expression of NLRC5 was determined by RT-PCR, Western blot and immunohistochemistry. Consequently, NLRC5 was overexpressed or knockdown by transfecting PEGFP-C2-NLRC5 or NLRC5-siRNA respectively in the reversal of hepatic fibrosis, and the expression of fibrogenic genes such as α-SMA and Col1α1 was quantified. The NF-κB activity was detected as well.
  
  
  RESULTS
  Immunohistochemistry, RT-PCR and Western blot analysis with liver tissues and primary HSCs showed that NLRC5 was highly expressed in hepatic fibrosis and correspondingly decreased in the reversal stage. The differential expression of NLRC5 was confirmed in vitro. Enforced NLRC5 expression increased the expression of α-SMA and Col1α1, and blockade of NLRC5 reduced the fibrotic response. While the opposite expression of phosphorylated NF-кB p65 and phospho-IκBα was found.
  
  
  CONCLUSIONS
  NLRC5 is differentially expressed in hepatic tissues and hepatic stellate cells during hepatic fibrosis and its reversal. All the data indicated that NLRC5 may play a crucial role in regulating the reversal of hepatic fibrosis through NF-κB signaling pathway.
authors.affiliation: School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Hefei 230032, China; Institute for Liver Diseases, Anhui Medical University, Hefei 230032, China. Electronic address: liuxuejiao0615@163.com.
authors.forename: Xuejiao
authors.initials: X
authors.lastname: Liu
authors.affiliation: School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Hefei 230032, China; Institute for Liver Diseases, Anhui Medical University, Hefei 230032, China.
authors.forename: Yuting
authors.initials: Y
authors.lastname: Wu
authors.affiliation: School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Hefei 230032, China; Institute for Liver Diseases, Anhui Medical University, Hefei 230032, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Hefei 230032, China; Institute for Liver Diseases, Anhui Medical University, Hefei 230032, China.
authors.forename: Wanxia
authors.initials: W
authors.lastname: Li
authors.affiliation: School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Hefei 230032, China; Institute for Liver Diseases, Anhui Medical University, Hefei 230032, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Huang
authors.affiliation: School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Hefei 230032, China; Institute for Liver Diseases, Anhui Medical University, Hefei 230032, China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Meng
authors.affiliation: School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Hefei 230032, China; Institute for Liver Diseases, Anhui Medical University, Hefei 230032, China; School of Pharmacy, Anhui Medical University, Mei Shan load, Hefei 230032, Anhui Province, China. Electronic address: lj@ahmu.edu.cn.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
mesh_terms: D000199:Actins / Q000235:genetics; D000818:Animals; D002252:Carbon Tetrachloride Poisoning / Q000235:genetics / Q000473:pathology; D024042:Collagen Type I / Q000235:genetics; D000090602:Collagen Type I, alpha 1 Chain; D055785:Gene Knockdown Techniques; D055166:Hepatic Stellate Cells / Q000378:metabolism; D020672:I-kappa B Proteins / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*; D008103:Liver Cirrhosis / Q000235:genetics* / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010766:Phosphorylation; D034741:RNA, Small Interfering / Q000235:genetics; D051996:Transcription Factor RelA / Q000378:metabolism; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000494:pharmacology
chemical_list: C558396:Acta2 protein, mouse; D000199:Actins; D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D020672:I-kappa B Proteins; D047908:Intracellular Signaling Peptides and Proteins; C549161:NLRC5 protein, mouse; D034741:RNA, Small Interfering; D051996:Transcription Factor RelA; D016212:Transforming Growth Factor beta
keywords: HSCs reversion; Hepatic fibrosis; NLRC5; Reversal of hepatic fibrosis