BALANCE OF EXPRESSION OF GENES-CODING FOR EXTRACELLULAR-MATRIX PROTEINS AND EXTRACELLULAR-MATRIX DEGRADING PROTEASES IN CHRONIC-PANCREATITIS

Chronic pancreatitis is characterized by proliferation of the extracel lular matrix and by increased deposition of interstitial extracellular matrix proteins (collagens type I and III, fibronectin). In this stud y we analyzed the balance of expression of mRNAs encoding extracellula r matrix components (collagens I, III and IV, laminin, fibronectin), e xtracellular matrix degrading metalloproteinases (MMP-1, -2 and -3) an d tissue inhibitors of metalloproteinases (TIMP-1 and -2) in chronic p ancreatitis (n = 8) and control pancreas (n = 7) by northern blot anal ysis. Transcripts for MMP-1 (interstitial collagenase), MMP-3 (stromel ysin) and TIMP-1 were not detectable in chronic pancreatitis and contr ol tissues. Steady-state levels of transcripts encoding extracellular matrix proteins, MMP-2 (72 kDa collagenase IV) and TIMP-2 were enhance d in 7 out of 8 chronic pancreatitis tissue samples and showed a large degree of variation between individual patients. Transcript levels co uld not be correlated to the histologically detectable degree of infla mmation and fibrosis or to the total amount of deposited collagen prot ein, which was high in all chronic pancreatitis tissue samples as dete rmined by a standard colorimetric procedure. Increased steady state le vels of transcripts encoding extracellular matrix proteins or extracel lular matrix degrading proteases may thus reflect the activity of proc esses involved in the remodeling of the gland during chronic inflammat ion. The precise role of overexpression of MMP-2 and its inhibitor TIM P-2 will have to be elucidated in further studies.