A Smad Signaling Network Regulates Islet Cell Proliferation

被引：62

作者：

El-Gohary, Yousef ^{[1
]}

Tulachan, Sidhartha ^{[2
]}

Wiersch, John ^{[1
,3
]}

Guo, Ping ^{[1
]}

Welsh, Carey ^{[4
]}

Prasadan, Krishna ^{[1
]}

Paredes, Jose ^{[1
]}

Shiota, Chiyo ^{[1
]}

Xiao, Xiangwei ^{[1
]}

Wada, Yoko ^{[5
]}

Diaz, Marilyn ^{[6
]}

Gittes, George ^{[1
]}

机构：

[1] Childrens Hosp Pittsburgh, Dept Surg, Div Pediat Surg, Pittsburgh, PA 15213 USA

[2] St Elizabeth Hlth Ctr, Dept Internal Med, Youngstown, OH USA

[3] Univ Texas Hlth Sci Ctr San Antonio, Sch Med, Dept Surg, San Antonio, TX 78229 USA

[4] Childrens Hosp Pittsburgh, Dept Pediat, Div Neonatol, Pittsburgh, PA 15213 USA

[5] Niigata Univ, Grad Sch Med & Dent Sci, Div Clin Nephrol & Rheumatol, Niigata, Japan

[6] Natl Inst Environm Hlth Sci, Lab Mol Genet, NIH, Res Triangle Pk, NC USA

来源：

DIABETES | 2014年 / 63卷 / 01期

基金：

美国国家卫生研究院;

关键词：

PANCREATIC BETA-CELLS; ENDOCRINE PANCREAS; EXOCRINE PANCREAS; MESENCHYMAL TRANSITION; DIFFERENTIAL ROLES; PRECURSOR CELLS; MOUSE PANCREAS; AR42J CELLS; IN-VITRO; GROWTH;

D O I：

10.2337/db13-0432

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Pancreatic -cell loss and dysfunction are critical components of all types of diabetes. Human and rodent -cells are able to proliferate, and this proliferation is an important defense against the evolution and progression of diabetes. Transforming growth factor- (TGF-) signaling has been shown to affect -cell development, proliferation, and function, but -cell proliferation is thought to be the only source of new -cells in the adult. Recently, -cell dedifferentiation has been shown to be an important contributory mechanism to -cell failure. In this study, we tie together these two pathways by showing that a network of intracellular TGF- regulators, smads 7, 2, and 3, control -cell proliferation after -cell loss, and specifically, smad7 is necessary for that -cell proliferation. Importantly, this smad7-mediated proliferation appears to entail passing through a transient, nonpathologic dedifferentiation of -cells to a pancreatic polypeptide-fold hormone-positive state. TGF- receptor II appears to be a receptor important for controlling the status of the smad network in -cells. These studies should help our understanding of properly regulated -cell replication.

引用

页码：224 / 236

页数：13