TRANSIENT EXPRESSION OF CLUSTERIN (SULFATED GLYCOPROTEIN-2) DURING DEVELOPMENT OF RAT PANCREAS

Clusterin has been known to play important roles not only in remodelin g damaged tissues, but also in tissue reorganization during embryonic development. In the present study, we have investigated the expression of clusterin in the endocrine pancreas during embryonic development. Although a weak immunoreaction was detected in some pancreatic primord ial cells at day 14 of gestation, distinct clusterin expression was id entified by immunocytochemistry and Northern blot analysis at the 16th day of gestation. Clusterin-producing cells, which corresponded to in sulin-containing cells, accounted for the major portion of the develop ing islet of Langerhans up to 18 days of gestation. Thereafter, cluste rin-producing cells display similar distribution and morphological fea tures to glucagon-producing cells. Clusterin expressed in the pancreas was shown by Western blot analysis to be a disulfide-linked heterodim er of 70 kDa with an alpha-subunit of 32 kDa. During early development al stages, however, we found that proteolytic internal cleavage of the clusterin molecule occurred from the 18th day of gestation. Only one 70 kDa band on the 16th day and two bands (32 kDa and 70 kDa) on the 1 8th day of gestation were detected by Western blot analysis even in re ducing conditions, while only a single 32 kDa band was detected on the second day after birth. The levels of clusterin mRNA in the pancreas transiently increased from the 16th day of gestation to the second day after birth, during the period when active cellular reorganization ta kes place to form the classic cellular features of the islet. Among va rious tissues (kidney, brain, liver, heart, lung and pancreas) the lev els of clusterin mRNA were the highest in the pancreas from the 18th d ay of gestation to the second day after birth. In contrast, the lowest expression was observed in adult pancreatic tissue. The higher expres sion of clusterin in developing pancreas must indicate its involvement in tissue organization during development.