title: Regulation of CFTR Expression and Arginine Vasopressin Activity Are Dependent on Polycystin-1 in Kidney-Derived Cells.
abstract: BACKGROUND
  Autosomal dominant polycystic kidney disease (ADPKD) is characterized by the development of multiple, progressive, fluid-filled renal cysts that distort the renal parenchyma, leading to end-stage renal failure, mainly after the fifth decade of life. ADPKD is caused by a mutation in the PKD1 or PKD2 genes that encode polycystin-1 (PC-1) and polycystin-2 (PC-2), respectively. PC-1 is an important regulator of several signaling pathways and PC-2 is a nonselective calcium channel. The CFTR chloride channel is responsible for driving net fluid secretion into the cysts, promoting cyst growth. Arginine vasopressin hormone (AVP), in turn, is capable of increasing cystic intracellular cAMP, contributing to cell proliferation, transepithelial fluid secretion, and therefore to disease progression. The aim of this study was to assess if AVP can modulate CFTR and whether PC-1 plays a role in this potential modulation.
  
  
  METHODS
  M1 cells, derived from mouse cortical collecting duct, were used in the current work. The cells were treated with 10-7 M AVP hormone and divided into two main groups: transfected cells superexpressing PC-1 (Transf) and cells not transfected (Ctrl). CFTR expression was assessed by immunodetection, CFTR mRNA levels were quantified by quantitative reverse transcription-polymerase chain reaction, and CFTR net ion transport was measured using the Ussing chamber technique.
  
  
  RESULTS
  AVP treatment increased the levels of CFTR protein and mRNA. CFTR short-circuit currents were also increased. However, when PC-1 was overexpressed in M1 cells, no increase in any of these parameters was detected.
  
  
  CONCLUSIONS
  CFTR chloride channel expression is increased by AVP in M1 cells and PC-1 is capable of regulating this modulation.
authors.affiliation: Laboratx00F3;rio de Fisiologia Celular e Molecular, Instituto de Biofx00ED;sica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Carolina Monteiro
authors.initials: CM
authors.lastname: de Lemos Barbosa
authors.forename: Jackson
authors.initials: J
authors.lastname: Souza-Menezes
authors.forename: Andressa Godoy
authors.initials: AG
authors.lastname: Amaral
authors.forename: Luiz Fernando
authors.initials: LF
authors.lastname: Onuchic
authors.forename: Liudmila
authors.initials: L
authors.lastname: Cebotaru
authors.forename: William B
authors.initials: WB
authors.lastname: Guggino
authors.forename: Marcelo M
authors.initials: MM
authors.lastname: Morales
mesh_terms: D000818:Animals; D050034:Antidiuretic Agents / Q000494:pharmacology; D001127:Arginine Vasopressin / Q000494:pharmacology*; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics / Q000378:metabolism*; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D007668:Kidney / Q000166:cytology; D051379:Mice; D018181:Mice, Inbred CFTR; D016891:Polycystic Kidney, Autosomal Dominant / Q000235:genetics / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D050396:TRPP Cation Channels / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
chemical_list: D050034:Antidiuretic Agents; D001127:Arginine Vasopressin; D000242:Cyclic AMP; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D012333:RNA, Messenger; D050396:TRPP Cation Channels