Proteomic changes during intestinal cell maturation in vivo.
Intestinal epithelial cells undergo progressive cell maturation as they migrate along the crypt-villus axis. To determine molecular signatures that define this process, proteins differentially expressed between the crypt and villus were identified by 2D-DIGE and MALDI-MS. Forty-six differentially expressed proteins were identified, several of which were validated by immunohistochemistry. Proteins upregulated in the villus were enriched for those involved in brush border assembly and lipid uptake, established features of differentiated intestinal epithelial cells. Multiple proteins involved in glycolysis were also upregulated in the villus, suggesting increased glycolysis is a feature of intestinal cell differentiation. Conversely, proteins involved in nucleotide metabolism, and protein processing and folding were increased in the crypt, consistent with functions associated with cell proliferation. Three novel paneth cell markers, AGR2, HSPA5 and RRBP1 were also identified. Notably, significant correlation was observed between overall proteomic changes and corresponding gene expression changes along the crypt-villus axis, indicating intestinal cell maturation is primarily regulated at the transcriptional level. This proteomic profiling analysis identified several novel proteins and functional processes differentially induced during intestinal cell maturation in vivo. Integration of proteomic, immunohistochemical, and parallel gene expression datasets demonstrate the coordinated manner in which intestinal cell maturation is regulated.
Chang
Jinsook
J
Center for Proteomics, Case Western Reserve University, Cleveland, OH 44106, USA.
Chance
Mark R
MR
Nicholas
Courtney
C
Ahmed
Naseem
N
Guilmeau
Sandra
S
Flandez
Marta
M
Wang
Donghai
D
Byun
Do-Sun
DS
Nasser
Shannon
S
Albanese
Joseph M
JM
Corner
Georgia A
GA
Heerdt
Barbara G
BG
Wilson
Andrew J
AJ
Augenlicht
Leonard H
LH
Mariadason
John M
JM
D000818:Animals; D004396:Coloring Agents; D015180:Electrophoresis, Gel, Two-Dimensional; D000091342:Endoplasmic Reticulum Chaperone BiP; D004798:Enzymes / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification; D005786:Gene Expression Regulation; D007413:Intestinal Mucosa / Q000737:chemistry / Q000166:cytology / Q000502:physiology*; D007421:Intestine, Small / Q000737:chemistry / Q000166:cytology / Q000502:physiology*; D008055:Lipids / Q000502:physiology; D051379:Mice; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification; D040901:Proteomics; D051381:Rats; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013256:Steroids / Q000378:metabolism
D004396:Coloring Agents; D000091342:Endoplasmic Reticulum Chaperone BiP; D004798:Enzymes; C000717248:Hspa5 protein, mouse; D008055:Lipids; D011506:Proteins; D013256:Steroids