PMID- 19589945
OWN - NLM
STAT- MEDLINE
DCOM- 20090910
LR  - 20240126
IS  - 1522-1547 (Electronic)
IS  - 0193-1857 (Print)
IS  - 0193-1857 (Linking)
VI  - 297
IP  - 3
DP  - 2009 Sep
TI  - Regeneration of intestinal stem/progenitor cells following doxorubicin treatment 
      of mice.
PG  - G461-70
LID - 10.1152/ajpgi.90446.2008 [doi]
AB  - The intestinal epithelium is in a constant state of renewal. The rapid turnover 
      of cells is fed by a hierarchy of transit amplifying and stem/progenitor cells 
      destined to give rise to the four differentiated epithelial lineages of the small 
      intestine. Doxorubicin (Dox) is a commonly used chemotherapeutic agent that 
      preferentially induces apoptosis in the intestinal stem cell zone (SCZ). We 
      hypothesized that Dox treatment would initially decrease "+4" intestinal stem 
      cell numbers with a subsequent expansion during mucosal repair. Temporal 
      assessment following Dox treatment demonstrated rapid induction of apoptosis in 
      the SCZ leading to a decrease in the number of intestinal stem/progenitor cells 
      as determined by flow cytometry for CD45(-) SP cells, and immunohistochemistry of 
      cells positive for putative +4 stem cell markers beta-cat(Ser552) and DCAMKL1. 
      Between 96 and 168 h postinjection, overall proliferation in the crypts increased 
      concomitant with increases in both absolute and relative numbers of goblet, 
      Paneth, and enteroendocrine cells. This regeneration phase was also associated 
      with increases of CD45(-) SP cells, beta-cat(Ser552)-positive cells, crypt 
      fission, and crypt number. We used Lgr5-lacZ mice to assess behavior of 
      Lgr5-positive stem cells following Dox and found no change in this cell 
      population. Lgr5 mRNA level was also measured and showed no change immediately 
      after Dox but decreased during the regeneration phase. Together these data 
      suggest that, following Dox-induced injury, expansion of intestinal stem cells 
      occurs during mucosal repair. On the basis of available markers this expansion 
      appears to be predominantly the +4 stem cell population rather than those of the 
      crypt base.
FAU - Dekaney, Christopher M
AU  - Dekaney CM
AD  - Department of Surgery, The University of North Carolina, Chapel Hill, North 
      Carolina 27599-7223, USA. dekaney@med.unc.edu
FAU - Gulati, Ajay S
AU  - Gulati AS
FAU - Garrison, Aaron P
AU  - Garrison AP
FAU - Helmrath, Michael A
AU  - Helmrath MA
FAU - Henning, Susan J
AU  - Henning SJ
LA  - eng
GR  - R01 DK069585/DK/NIDDK NIH HHS/United States
GR  - T32 DK07664/DK/NIDDK NIH HHS/United States
GR  - P30 DK56338/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20090709
PL  - United States
TA  - Am J Physiol Gastrointest Liver Physiol
JT  - American journal of physiology. Gastrointestinal and liver physiology
JID - 100901227
RN  - 0 (Antibiotics, Antineoplastic)
RN  - 0 (CTNNB1 protein, mouse)
RN  - 0 (Lgr5 protein, mouse)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, G-Protein-Coupled)
RN  - 0 (beta Catenin)
RN  - 80168379AG (Doxorubicin)
RN  - EC 2.7.1.11 (Doublecortin-Like Kinases)
RN  - EC 2.7.11.1 (Dclk1 protein, mouse)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 3.1.3.48 (Leukocyte Common Antigens)
RN  - EC 3.1.3.48 (Ptprc protein, mouse)
SB  - IM
MH  - Animals
MH  - Antibiotics, Antineoplastic/administration & dosage/*toxicity
MH  - Apoptosis/*drug effects
MH  - Cell Lineage
MH  - Cell Proliferation/*drug effects
MH  - Doublecortin-Like Kinases
MH  - Doxorubicin/administration & dosage/*toxicity
MH  - Female
MH  - Injections, Intraperitoneal
MH  - Intestinal Mucosa/*drug effects/metabolism/pathology
MH  - Intestine, Small/*drug effects/metabolism/pathology
MH  - Jejunum/drug effects/pathology
MH  - Leukocyte Common Antigens/analysis
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Protein Serine-Threonine Kinases/metabolism
MH  - RNA, Messenger/metabolism
MH  - Receptors, G-Protein-Coupled/genetics/metabolism
MH  - Regeneration/*drug effects
MH  - Stem Cells/*drug effects/metabolism/pathology
MH  - Time Factors
MH  - beta Catenin/metabolism
PMC - PMC2739827
EDAT- 2009/07/11 09:00
MHDA- 2009/09/11 06:00
PMCR- 2010/09/01
CRDT- 2009/07/11 09:00
PHST- 2009/07/11 09:00 [entrez]
PHST- 2009/07/11 09:00 [pubmed]
PHST- 2009/09/11 06:00 [medline]
PHST- 2010/09/01 00:00 [pmc-release]
AID - 90446.2008 [pii]
AID - GI-90446-2008 [pii]
AID - 10.1152/ajpgi.90446.2008 [doi]
PST - ppublish
SO  - Am J Physiol Gastrointest Liver Physiol. 2009 Sep;297(3):G461-70. doi: 
      10.1152/ajpgi.90446.2008. Epub 2009 Jul 9.