title: Persistent destruction of the basement membrane of the pancreatic duct contributes to progressive acinar atrophy in rats with experimentally induced pancreatitis.
abstract: OBJECTIVE
  The imbalance between synthesis and degradation of extracellular matrix (ECM) proteins is a characteristic feature in chronic pancreatitis. We evaluated the relationship between type IV collagen structure in the basement membrane (BM) and the development of acinar atrophy or the regeneration from acinar injury.
  
  
  METHODS
  Three different models of pancreatitis were induced in rats by repetitive intraperitoneal injections of 500 mg/100 g body weight of arginine (Arg) or 20 microg/kg body weight of caerulein (Cn) or a single retrograde intraductal infusion of 40 microL/100 g body weight of 3% sodium taurocholate (NaTc). We examined the changes in type IV collagen structure by immunostaining, and the serial changes in the gelatinolytic activity of pro- and active matrix metalloproteinase-2 by zymography in these models of pancreatitis.
  
  
  RESULTS
  The pancreas appeared to be histologically normal on day 35 after the first intraperitoneal Cn injection and on day 42 after intraductal infusion of NaTc, whereas 85% to 90% of acinar tissue was replaced by fatty tissue and dilated pancreatic ducts on day 54 after the first intraperitoneal Arg injection. Immunoreactivity for type IV collagen appeared as a discontinuous line along the BM of ducts, vessels, tubular complexes, and acinar cells on day 40 in Arg-induced pancreatitis, whereas it was detected as a continuous line along the BM on day 35 in Cn-induced pancreatitis and on day 42 in NaTc-induced pancreatitits. Gelatinolytic activity of active MMP-2 increased significantly from day 13 to day 40 after the first intraperitoneal Arg injection, whereas it decreased to the baseline level on day 35 after the first intraperitoneal Cn injection and on day 42 after intraductal infusion of NaTc.
  
  
  CONCLUSIONS
  Our findings indicate that a long-term increase in gelatinolytic activity of active MMP-2 in Arg-induced pancreatitis causes continuous disorganization of type IV collagen in the BM and progressive acinar atrophy, whereas a transient increase in gelatinolytic activity of active MMP-2 is involved in the regeneration of type IV collagen structure in the BM and recovery from acinar injury.
authors.affiliation: Third Department of Internal Medicine, University of Occupational and Environmental Health, Japan, School of Medicine, Kitakyushu 807-8555, Japan.
authors.forename: Taizo
authors.initials: T
authors.lastname: Yamaguchi
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Kihara
authors.forename: Masashi
authors.initials: M
authors.lastname: Taguchi
authors.forename: Yoshikuni
authors.initials: Y
authors.lastname: Nagashio
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Tashiro
authors.forename: Hayato
authors.initials: H
authors.lastname: Nakamura
authors.forename: Makoto
authors.initials: M
authors.lastname: Otsuki
mesh_terms: D000818:Animals; D001284:Atrophy; D001485:Basement Membrane / Q000473:pathology*; D015152:Blotting, Northern; D024141:Collagen Type IV / Q000032:analysis / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D010179:Pancreas / Q000473:pathology*; D010183:Pancreatic Ducts / Q000473:pathology*; D010195:Pancreatitis / Q000473:pathology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar
chemical_list: D024141:Collagen Type IV; D012333:RNA, Messenger; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9