PMID- 36705791
OWN - NLM
STAT- MEDLINE
DCOM- 20230330
LR  - 20230705
IS  - 1573-4978 (Electronic)
IS  - 0301-4851 (Linking)
VI  - 50
IP  - 4
DP  - 2023 Apr
TI  - KAP1 modulates osteogenic differentiation via the ERK/Runx2 cascade in vascular 
      smooth muscle cells.
PG  - 3217-3228
LID - 10.1007/s11033-022-08225-z [doi]
AB  - BACKGROUND: Osteoblast phenotypic transition in vascular smooth muscle cells 
      (VSMCs) has been unveiled as a common cause of vascular calcification (VC). 
      Kruppel-Associated Box (KRAB)-Associated Protein 1(KAP1) is a transcriptional 
      corepressor that modulates various intracellular pathological processes from gene 
      expression to DNA repair to signal transduction. However, the function and 
      mechanism of KAP1 on the osteoblastic differentiation of VSMCs have not been 
      evaluated yet. METHODS AND RESULTS: We demonstrate that the expression of KAP1 in 
      VSMCs is significantly enhanced in vivo and in vitro calcification models. 
      Downregulating the expression of KAP1 suppresses the osteoblast phenotypic 
      transition of VSMCs, which is indicated by a decrease in the expression of 
      osteoblast marker collagenase type I (COL I) and an increase in the expression of 
      VSMC marker alpha-smooth muscle actin (alpha-SMA). Conversely, exogenous overexpression 
      of KAP1 could promote osteoblast phenotypic transition of VSMCs. Moreover, KAP1 
      upregulated the expression of RUNX family transcription factor 2 (Runx2), an 
      inducer of osteoblast that positively regulates many osteoblast-related genes, 
      such as COL I. Evaluation of the potential mechanism demonstrated that KAP1 
      promoted osteoblast phenotypic transition of VSMCs by activating the 
      extracellular regulated protein kinases (ERK) signaling pathway, which could 
      activate Runx2. In support of this finding, KAP1-induced cell osteoblast 
      phenotypic transition is abolished by treatment with PD0325901, a specific ERK 
      inhibitor. CONCLUSIONS: The present study suggested that KAP1 participated in the 
      osteoblast differentiation of VSMCs via the ERK/Runx2 cascade and served as a 
      potential diagnostics and therapeutics target for vascular calcification.
CI  - (c) 2023. The Author(s), under exclusive licence to Springer Nature B.V.
FAU - Bai, Weiwei
AU  - Bai W
AD  - Department of Nephrology, The Fourth Hospital of Hebei Medical University, Hebei 
      Clinical Research Center for Chronic Kidney Disease, Hebei Key Laboratory of 
      Vascular Calcification in Kidney Disease, Shijiazhuang, P.R. China.
FAU - Cheng, Meijuan
AU  - Cheng M
AD  - Department of Nephrology, The Fourth Hospital of Hebei Medical University, Hebei 
      Clinical Research Center for Chronic Kidney Disease, Hebei Key Laboratory of 
      Vascular Calcification in Kidney Disease, Shijiazhuang, P.R. China.
FAU - Jin, Jingjing
AU  - Jin J
AD  - Department of Nephrology, The Fourth Hospital of Hebei Medical University, Hebei 
      Clinical Research Center for Chronic Kidney Disease, Hebei Key Laboratory of 
      Vascular Calcification in Kidney Disease, Shijiazhuang, P.R. China.
FAU - Zhang, Dongxue
AU  - Zhang D
AD  - Department of Nephrology, The Fourth Hospital of Hebei Medical University, Hebei 
      Clinical Research Center for Chronic Kidney Disease, Hebei Key Laboratory of 
      Vascular Calcification in Kidney Disease, Shijiazhuang, P.R. China.
FAU - Li, Lanmei
AU  - Li L
AD  - Department of Nephrology, The Fourth Hospital of Hebei Medical University, Hebei 
      Clinical Research Center for Chronic Kidney Disease, Hebei Key Laboratory of 
      Vascular Calcification in Kidney Disease, Shijiazhuang, P.R. China.
FAU - Bai, Yaling
AU  - Bai Y
AD  - Department of Nephrology, The Fourth Hospital of Hebei Medical University, Hebei 
      Clinical Research Center for Chronic Kidney Disease, Hebei Key Laboratory of 
      Vascular Calcification in Kidney Disease, Shijiazhuang, P.R. China.
FAU - Xu, Jinsheng
AU  - Xu J
AD  - Department of Nephrology, The Fourth Hospital of Hebei Medical University, Hebei 
      Clinical Research Center for Chronic Kidney Disease, Hebei Key Laboratory of 
      Vascular Calcification in Kidney Disease, Shijiazhuang, P.R. China. 
      xjs5766@126.com.
LA  - eng
GR  - 20377704D/Hebei Province Key Research and Development Project/
PT  - Journal Article
DEP - 20230127
PL  - Netherlands
TA  - Mol Biol Rep
JT  - Molecular biology reports
JID - 0403234
RN  - 0 (Core Binding Factor Alpha 1 Subunit)
RN  - 0 (RUNX2 protein, human)
RN  - 0 (Cytoskeletal Proteins)
SB  - IM
EIN - Mol Biol Rep. 2023 Jul;50(7):6305. PMID: 37233915
EIN - Mol Biol Rep. 2023 Sep;50(9):7949. PMID: 37402068
MH  - Humans
MH  - Cell Differentiation
MH  - Cells, Cultured
MH  - Core Binding Factor Alpha 1 Subunit/genetics/metabolism
MH  - Muscle, Smooth, Vascular/metabolism
MH  - Myocytes, Smooth Muscle/metabolism
MH  - *Osteogenesis/genetics
MH  - Signal Transduction
MH  - *Vascular Calcification/metabolism
MH  - Cytoskeletal Proteins/metabolism
MH  - MAP Kinase Signaling System
OTO - NOTNLM
OT  - ERK
OT  - KAP1
OT  - Osteoblast differentiation
OT  - Runx2
OT  - Vascular calcification
EDAT- 2023/01/28 06:00
MHDA- 2023/03/29 06:05
CRDT- 2023/01/27 11:27
PHST- 2022/11/08 00:00 [received]
PHST- 2022/12/20 00:00 [accepted]
PHST- 2023/03/29 06:05 [medline]
PHST- 2023/01/28 06:00 [pubmed]
PHST- 2023/01/27 11:27 [entrez]
AID - 10.1007/s11033-022-08225-z [pii]
AID - 10.1007/s11033-022-08225-z [doi]
PST - ppublish
SO  - Mol Biol Rep. 2023 Apr;50(4):3217-3228. doi: 10.1007/s11033-022-08225-z. Epub 
      2023 Jan 27.