title: Up-regulated FHL1 expression maybe involved in the prognosis of Hirschsprung's disease.
abstract: BACKGROUND
  In a subset of patients with Hirschsprung's disease (HSCR), gastrointestinal motor dysfunction persisted long after surgical correction. Gastrointestinal motility is achieved through the coordinated activity of the enteric nervous system, interstitial cells of Cajal, and smooth muscle (SMC) cells. Inhibition of four-and-a-half LIM protein-1 (Fhl1) expression by siRNA significantly decreases pulmonary artery SMCs migration and proliferation. Furthermore when up-expressing FHL1 in atrial myocytes, K (+) current density markedly increases, therefore changing myocytes' response to an electrical stimulus. However whether FHL1 in colon SMCs (the final effector organ) influences intestinal motility in HSCR patients has not been clarified.
  
  
  METHODS
  FHL1 mRNA and protein expressions were analyzed in 32 HSCR colons and 4 normal colons.
  
  
  RESULTS
  Smooth muscle layers were thicken and disorganized in HSCR. FHL1 was expressed in the ganglion cells of the myenteric plexus, submucosa, as well as in the longitudinal and circular muscle layer of the ganglionic colon. FHL1 mRNA relative expression level in aganglionic colons was 1.06 ± 0.49 (ganglionic colon relative expression level was 1) (P=0.44). FHL1 protein gray level relative to GAPDH in normal colons was 0.83 ± 0.09. FHL1 expression level in ganglionic colon (1.66 ± 0.30) or aganglionic colon (1.81 ± 0.35) was significantly higher than that in normal colons (P=0.045 and P=0.041, respectively). Meanwhile, we found FHL1 expression in aganglionic colon was slightly stronger than that in ganglionic colon (P=0.036).
  
  
  CONCLUSIONS
  These data suggested that up-regulated FHL1 in smooth muscle in HSCR might be associated with intestinal wall remodeling in HSCR and might be one of the risk factors for gastrointestinal motor dysfunction.
authors: Key laboratory of Health Ministry for Congenital Malformation, Shengjing Hospital, China Medical University, Shen yang, 110004, P.R. China.
authors: Li-Li
authors: LL
authors: Wang
authors: Key laboratory of Health Ministry for Congenital Malformation, Shengjing Hospital, China Medical University, Shen yang, 110004, P.R. China.
authors: Hui
authors: H
authors: Gu
authors: Key laboratory of Health Ministry for Congenital Malformation, Shengjing Hospital, China Medical University, Shen yang, 110004, P.R. China.
authors: Yang
authors: Y
authors: Fan
authors: Key laboratory of Health Ministry for Congenital Malformation, Shengjing Hospital, China Medical University, Shen yang, 110004, P.R. China.
authors: Yi
authors: Y
authors: Zhang
authors: Key laboratory of Health Ministry for Congenital Malformation, Shengjing Hospital, China Medical University, Shen yang, 110004, P.R. China.
authors: Di
authors: D
authors: Wu
authors: Key laboratory of Health Ministry for Congenital Malformation, Shengjing Hospital, China Medical University, Shen yang, 110004, P.R. China.
authors: Jia-Ning
authors: JN
authors: Miao
authors: Key laboratory of Health Ministry for Congenital Malformation, Shengjing Hospital, China Medical University, Shen yang, 110004, P.R. China.
authors: Tian-Chu
authors: TC
authors: Huang
authors: Key laboratory of Health Ministry for Congenital Malformation, Shengjing Hospital, China Medical University, Shen yang, 110004, P.R. China.
authors: Hui
authors: H
authors: Li
authors: Key laboratory of Health Ministry for Congenital Malformation, Shengjing Hospital, China Medical University, Shen yang, 110004, P.R. China.
authors: Zheng-Wei
authors: ZW
authors: Yuan
mesh_terms: D002465:Cell Movement / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D003106:Colon / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005769:Gastrointestinal Motility / Q000235:genetics; D005786:Gene Expression Regulation; D006627:Hirschsprung Disease / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007223:Infant; D047908:Intracellular Signaling Peptides and Proteins / Q000096:biosynthesis* / Q000235:genetics; D060588:LIM Domain Proteins / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D032342:Muscle Cells / Q000378:metabolism / Q000473:pathology; D009124:Muscle Proteins / Q000096:biosynthesis* / Q000235:genetics; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000473:pathology; D011379:Prognosis; D011651:Pulmonary Artery / Q000378:metabolism / Q000473:pathology; D034741:RNA, Small Interfering / Q000235:genetics
chemical_list: C101149:FHL1 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D060588:LIM Domain Proteins; D009124:Muscle Proteins; D034741:RNA, Small Interfering
keywords: FHL1; Hirschsprung's disease; expression; prognosis; smooth muscle