title: Functional role of NKX2-5 and Smad6 expression in developing rheumatic heart disease.
abstract: OBJECTIVE
  Rheumatic heart disease (RHD) results due to the cross reaction of the host immune system when it develops immunity against group A streptococcal infection. This autoimmune disease progress with different pathological conditions and the genes associated with it are still less understood.
  
  
  METHODS
  To understand the role of NKX2-5 and Smad-6 in developing an RHD, we successfully developed RHD model using BALB/c mice and we evaluate the expression of NKX2-5 and Smad-6 in different conditions.
  
  
  RESULTS
  The disease conditions are confirmed through histological sectioning of RHD heart tissue with its associated Aschoff bodies. The histological of control heart tissue in the absence of NKX2-5 looks abnormal with an enlarged nucleus and in the absence of Smad-6 the solid nature of heart tissue loosens. The mice developed a complex form of acute RHD with tissue hardening in the absence of either NKX2-5 or Smad-6 which are confirmed in NKX2-5 or Smad-6 null mice. Immunohistochemical studies reveal that the NKX2-5 and Smad-6 expression get down regulated on developing with RHD. Through experiments, we detected that both Nkx2-5 and Smad-6 are both inter-dependable and it negatively regulated each other by inhibiting them. In the absence of NKX2-5 or Smad-6, a severe form of RHD is observed together with down-regulation of either NKX2-5 or Smad-6.
  
  
  CONCLUSIONS
  The present investigation of NKX2-5 and Smad-6 in RHD provides a new insight of data that helps to understand the disease pathogenesis.
authors.affiliation: Department of Cardiology, Huaihe Hospital of Henan University, Kaifeng, Henan Province, China. liyanming199@hotmail.com.
authors.forename: X-L
authors.initials: XL
authors.lastname: Lu
authors.forename: X-L
authors.initials: XL
authors.lastname: Yao
authors.forename: C-Y
authors.initials: CY
authors.lastname: Yan
authors.forename: Q-L
authors.initials: QL
authors.lastname: Wan
authors.forename: Y-M
authors.initials: YM
authors.lastname: Li
mesh_terms: D000818:Animals; D005260:Female; D005786:Gene Expression Regulation; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D012214:Rheumatic Heart Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051905:Smad6 Protein / Q000096:biosynthesis* / Q000235:genetics; D013290:Streptococcal Infections / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins; C484469:Nkx2-5 protein, mouse; D051905:Smad6 Protein; C497803:Smad6 protein, mouse; D014157:Transcription Factors