Avtor/Urednik		Miralles, Francisco; Battelino, Tadej; Czernichow, Paul; Scharfmann, Raphael
Naslov		TGF-beta plays a key role in morphogenesis of the pancreatic islets of Langerhans by controlling the activity of the matrix metalloproteinase MMP-2
Tip		članek
Vir		J Cell Biol
Vol. in št.		Letnik 143, št. 3
Leto izdaje		1998
Obseg		str. 827-36
Jezik		eng
Abstrakt		Islets of Langerhans are microorgans scattered througout in pancreas, and are responsible for synthesizing and secreting pancreatic hormones. While progress has recently been made concerning cell differentiation of the islets of Langerhans, the mechanism controlling islets morphogenesis is not know. It is thought that these islets are formed by mature cell association, first differentiating in the primitive pancreatic epithelium, then migrating in the extracellular matrix, and finally associating into islets of Langerhans. This mechanism suggests that the extracellurar matrix has to be degraded for proper islet morphogenesis. We demonstrated in the present study that during rat pancreatic development, matrix metalloproteinase 2 (MMP-2) is activated in vivo between E17 and E19 when islets morphogenesis occurs. We next demonstrated that when E12.5 pancreatic epithelia develop in vitro. MMP -2 is activated in an in vitro model that recapitulates endocrine pancreas development (Miralles, F.,P. Czernichow, and R. Scharfmann. 1998). Development. 125: 1017-1024). On the other hand, islet morpohogenesis was impaired when MMP-2 activity was inhibited. We next demonstrated that exogenous TGF beta1 positively controls both islets morphogenesis and MMP-2 activity. Finally, we demonsrtated that both islets morphogenesis and MMP-2 activation were abolished in the presence of a pan-specific TGF-beta neutralizing antibody. Taken together, these observations demonstrate that in vitro, TGF-beta is a key activator of pancreatic MMP/2, and that MMP-2 activity is necessary for islets morphogenesis.
Deskriptorji		ISLETS OF LANGERHANS TRANSFORMING GROWTH FACTOR BETA METALLOPROTEINASES GELATINASES RATS, WISTAR CELLS, CULTURED EPITHELIUM POLYMERASE CHAIN REACTION GENE EXPRESSION RNA-DIRECTED DNA POLYMERASE