title: Proteolytic tailoring of the heat shock protein 70 and its implications in the pathogenesis of endometriosis.
abstract: OBJECTIVE
  To investigate the mechanism underlying the appearance of a 20-kd HSP70 fragment and its consequences in the ectopic endometrium of endometriosis patients.
  
  
  METHODS
  Experimental study.
  
  
  METHODS
  Research institute and obstetrics and gynecology clinic.
  
  
  METHODS
  Participants with (n = 18) and without (n = 20) endometriosis.
  
  
  METHODS
  None.
  
  
  METHODS
  Reverse-transcription polymerase chain reaction, protease assays, and in silico tools were used to investigate the origin of the 20-kd HSP70 fragment. Immunocolocalization studies were carried out to determine whether subtilisin/kexin isozyme 1 (SKI-1) and HSP70 are colocalized. Expression and localization of surrogate markers of inflammation, such as nuclear factor NF-κB and interleukin IL-6 were examined by immunoblotting and in situ studies.
  
  
  RESULTS
  HSP70 is posttranslationally processed into a 20-kd fragment by SKI-1, a protease of the subtilisin family, in ectopic endometrium (ECE). Immunocolocalization studies revealed spatial proximity of SKI-1 and HSP70 in ECE. Furthermore, ECE demonstrated nuclear localization of the transcription factor, NF-κB and high expression of its target protein, IL-6.
  
  
  CONCLUSIONS
  This study hints at the possible mechanisms underlying the trimming of HSP70 in ECE and also at the role of proteases in the pathogenesis of endometriosis. The possible repercussions of HSP70 fragmentation include dysregulation of key regulatory proteins, resulting in the escalation of inflammatory events in endometriotic lesions.
authors.affiliation: Department of Gamete Immunobiology, National Institute for Research in Reproductive Health, Indian Council of Medical Research, Parel, Mumbai, India.
authors.forename: Nina
authors.initials: N
authors.lastname: Chehna-Patel
authors.forename: Neeta
authors.initials: N
authors.lastname: Warty
authors.forename: Geetanjali
authors.initials: G
authors.lastname: Sachdeva
authors.forename: Vrinda
authors.initials: V
authors.lastname: Khole
mesh_terms: D000328:Adult; D001483:Base Sequence; D004715:Endometriosis / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D010532:Peritoneal Diseases / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D043484:Proprotein Convertases / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012697:Serine Endopeptidases / Q000378:metabolism; D020860:Subtilisin / Q000378:metabolism; D014018:Tissue Distribution; D055815:Young Adult
chemical_list: D018840:HSP70 Heat-Shock Proteins; D011994:Recombinant Proteins; D043484:Proprotein Convertases; D012697:Serine Endopeptidases; C115575:membrane-bound transcription factor peptidase, site 1; D020860:Subtilisin