PMID- 32269712
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200928
IS  - 1943-8141 (Print)
IS  - 1943-8141 (Electronic)
IS  - 1943-8141 (Linking)
VI  - 12
IP  - 3
DP  - 2020
TI  - P27 deletion enhances hematopoiesis by paracrine action of IL22 secreted from 
      bone marrow mesenchymal stem cells.
PG  - 787-799
AB  - Previous studies have reported that p27 deletion stimulates the proliferation of 
      bone marrow mesenchymal stem cells (BM-MSCs) and their differentiation into 
      osteoblasts, it also increases bone marrow hematopoietic progenitor cells (HPCs). 
      However, it is unknown whether the enhanced hematopoiesis induced by p27 
      deficiency was associated with releasing hematopoietic stem cell (HSC) and HPC 
      supporting factors by BM-MSCs. To answer this question, we cultured the BM-MSCs 
      from wild-type (WT) or p27 knockout (KO) mice, analyzed their proliferation, 
      apoptosis and osteogenesis and harvested their conditioned medium (CM); We also 
      cultured the bone marrow cells (BMCs) with normal medium or CM from WT or KO 
      BM-MSCs and analyzed changes of HSCs and HPCs and colony forming cells (CFCs). 
      Our results showed that the proliferation and osteogenic differentiation of 
      BM-MSCs were increased significantly and their apoptosis was reduced 
      significantly in p27 deficient mice. Simultaneously, we demonstrated that the CM 
      from p27 deficient BM-MSCs stimulated the expansion of HSCs/HPCs more 
      dramatically than that from WT BM-MSCs. Five 2-fold up-regulated proteins were 
      identified in the CM from p27 deficient BM-MSCs by protein chip assays, including 
      interleukin-22 (IL-22), transforming growth factor-beta type I receptor, tumor 
      necrosis factor-related Apoptosis-inducing ligands, VE-cadherin and vascular 
      endothelial growth factor B. We confirmed that expression of IL22 at both mRNA 
      and protein levels were up-regulated significantly in p27 deficient BM-MSCs. The 
      treatment of IL22 increased the percentages of HSCs and HPCs in BMC cultures and 
      the number of CFCs in the colony formation assay, whereas the increased HSC/HPC 
      expansion induced by the CM derived from p27 deficient BM-MSCs was blocked by the 
      addition of anti-IL22 antibody in a dose dependent manner. We also found that the 
      percentages of IL22R1, Stat3 and p-Stat3-S727 positive HSCs and HPCs were 
      increased significantly in p27 deficient BMCs. Our findings in this study 
      indicate that p27 deficiency stimulates HSC/HPC expansion by increasing secretion 
      of IL22 by BM-MSCs and activating IL22-Stat3 signaling in HSCs and HPCs.
CI  - AJTR Copyright (c) 2020.
FAU - Lu, Ruinan
AU  - Lu R
AD  - Department of Hematology, The First Affiliated Hospital of Nanjing Medical 
      University Nanjing, China.
AD  - Research Center for Bone and Stem Cells, Key Laboratory for Aging & Disease, 
      Nanjing Medical University Nanjing 211166, China.
FAU - Wang, Qian
AU  - Wang Q
AD  - Department of Human Anatomy, School of Medicine, Jiangsu University Zhenjiang 
      212013, China.
FAU - Li, Jianyong
AU  - Li J
AD  - Department of Hematology, The First Affiliated Hospital of Nanjing Medical 
      University Nanjing, China.
FAU - Miao, Dengshun
AU  - Miao D
AD  - The Research Center for Aging, Friendship Affiliated Plastic Surgery Hospital of 
      Nanjing Medical University Nanjing, China.
AD  - Research Center for Bone and Stem Cells, Key Laboratory for Aging & Disease, 
      Nanjing Medical University Nanjing 211166, China.
LA  - eng
PT  - Journal Article
DEP - 20200315
PL  - United States
TA  - Am J Transl Res
JT  - American journal of translational research
JID - 101493030
PMC - PMC7137050
OTO - NOTNLM
OT  - IL22-Stat3 signaling
OT  - bone marrow mesenchymal stem cells
OT  - hematopoietic progenitor cells
OT  - hematopoietic stem cells
OT  - p27 deficiency
COIS- None.
EDAT- 2020/04/10 06:00
MHDA- 2020/04/10 06:01
PMCR- 2020/03/15
CRDT- 2020/04/10 06:00
PHST- 2019/09/02 00:00 [received]
PHST- 2019/10/12 00:00 [accepted]
PHST- 2020/04/10 06:00 [entrez]
PHST- 2020/04/10 06:00 [pubmed]
PHST- 2020/04/10 06:01 [medline]
PHST- 2020/03/15 00:00 [pmc-release]
PST - epublish
SO  - Am J Transl Res. 2020 Mar 15;12(3):787-799. eCollection 2020.