GDDR and GKN1 Are Selectively Expressed in the Pancreatic Ducts and Represent New Markers of Pancreas Regeneration.

Dodge, Rikke R.; Bonner-Weir, Susan; Sharma, Arun

In response to a variety of regenerative signals pancreatic ductal cells initiate the process of regeneration. To harvest the true potential of pancreatic regeneration for the treatment of diabetes, it is essential to identify duct-specific genes that are differentially regulated by regenerative signals. To this end, we analyzed gene expression profiles of pancreatic duets isolated after sham surgery or 90% partial pancreatectomy (Px) and identified genes that are selectively expressed in the ducts and differentially regulated in response to regeneration. Gastrokine-1 (GKN1) and down regulated in gastric cancer (GDDR) were identified as the two most differentially and highly expressed genes. RT-PCR and immunostaining confirmed the microarray data. GKN1 and GDDR immunostaining were restricted to ducts in sections from mouse, rat and human pancreases. One day following Px, at the time of increased replication and induction of PDX-1 protein, expression of these genes were substantially reduced in the common pancreatic duct (CPD) by immunohistochemistry. By 7 days post Px, CPD, now quiescent and without PDX-1 protein expression, re-expresses GKN1 and GDDR. These results demonstrate that GKN1 and GDDR are markers of pancreatic ducts that are down regulated in response to regenerative signal-induced dedifferentiation of ductal cells. Further characterization of these genes could lead to identification of signals that regulate pancreatic regeneration.

PANCREATIC regeneration; TREATMENT of diabetes; GENE expression; PANCREATECTOMY; IMMUNOHISTOCHEMISTRY; GENES

Diabetes, 2007, Vol 56, pA418

0012-1797

Academic Journal