Molecular mechanism of pancreatic β-cell adaptive proliferation: studies during pregnancy in rats and in vitro.
There is a widespread interest in defining factors and mechanisms that stimulate proliferation of pancreatic islet β-cells. Pregnancy is a special period when the pancreatic islet displays a highly reproducible physiological proliferation. However, the molecular mechanism of β-cell proliferation during pregnancy is unclear. Here, we used cDNA expression array to explore gene expression profiles of islet at various stages of pregnancy in rats. Differentially expressed genes related to islet proliferation were screened by bioinformatics methods, and further verified by real-time PCR, RT-PCR, and Western blotting. Compared with control group, expressions of hundreds of genes were changed during pregnancy. The differentially expressed genes related to islet proliferation were mainly distributed in three groups: genes involved in transcription regulator activity, genes involved in apoptosis or tumor, and genes for Wnt signaling pathway. Among these genes, expressions of Nupr1, Atf3, Btg2, β-catenin, and c-Myc mRNA were up-regulated during pregnancy. A prominent expression of Nupr1 and Atf3 protein was observed in islets on day 10.5 of pregnancy, i.e., with earlier time phases than proliferation peak. Moreover, we found that prolactin (PRL) can increase the proliferation of β-cell in vitro, which is accompanied by up-regulation of Atf3 and Nupr1, indicating that they may play a crucial role in PRL-induced pancreatic β-cell growth. In conclusion, our results suggest that the transcription factor Nupr1, Atf3, and Wnt pathway may play an important role in adaptive proliferation of pancreatic islets during pregnancy in rats.
Department of Endocrinology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Guofang
G
Chen
Cuiping
C
Liu
Ying
Y
Xue
Xiaodong
X
Mao
Kuanfeng
K
Xu
Chao
C
Liu
D051700:Activating Transcription Factor 3 / Q000235:genetics / Q000378:metabolism; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D049109:Cell Proliferation; D019295:Computational Biology / Q000379:methods; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000378:metabolism*; D007515:Islets of Langerhans / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D009924:Organ Culture Techniques; D011247:Pregnancy; D011388:Prolactin / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism
D051700:Activating Transcription Factor 3; D051792:Basic Helix-Loop-Helix Proteins; D009363:Neoplasm Proteins; D011388:Prolactin; D012333:RNA, Messenger; D051153:Wnt Proteins; C497108:Atf3 protein, rat; C109741:Nupr1 protein, rat