PMID- 29415884
OWN - NLM
STAT- MEDLINE
DCOM- 20191028
LR  - 20220408
IS  - 2379-3708 (Electronic)
IS  - 2379-3708 (Linking)
VI  - 3
IP  - 3
DP  - 2018 Feb 8
TI  - TNF receptor-activated factor 2 mediates cardiac protection through noncanonical 
      NF-kappaB signaling.
LID - 98278 [pii]
LID - 10.1172/jci.insight.98278 [doi]
LID - e98278
AB  - To elucidate the mechanisms responsible for cytoprotective effects of TNF 
      receptor-activated factor 2 (TRAF2) in the heart, we employed genetic gain- and 
      loss-of-function studies ex vivo and in vivo in mice with cardiac-restricted 
      overexpression of TRAF2 (Myh6-TRAF2LC). Crossing Myh6-TRAF2LC mice with mice 
      lacking canonical signaling (Myh6-TRAF2LC/Myh6-IkappaBalphaDeltaN) abrogated the 
      cytoprotective effects of TRAF2 ex vivo. In contrast, inhibiting the JAK/STAT 
      pathway did not abrogate the cytoprotective effects of TRAF2. Transcriptional 
      profiling of WT, Myh6-TRAF2LC, and Myh6-TRAF2LC/Myh6-IkappaBalphaDeltaN mouse hearts 
      suggested that the noncanonical NF-kappaB signaling pathway was upregulated in the 
      Myh6-TRAF2LC mouse hearts. Western blotting and ELISA for the NF-kappaB family 
      proteins p50, p65, p52, and RelB on nuclear and cytoplasmic extracts from naive 
      12-week-old WT, Myh6-TRAF2LC, and Myh6-TRAF2LC/Myh6-IkappaBalphaDeltaN mouse hearts showed 
      increased expression levels and increased DNA binding of p52 and RelB, whereas 
      there was no increase in expression or DNA binding of the p50 and p65 subunits. 
      Crossing Myh6-TRAF2LC mice with RelB-/+ mice (Myh6-TRAF2LC/RelB-/+) attenuated 
      the cytoprotective effects of TRAF2 ex vivo and in vivo. Viewed together, these 
      results suggest that crosstalk between the canonical and noncanonical NF-kappaB 
      signaling pathways is required for mediating the cytoprotective effects of TRAF2.
FAU - Evans, Sarah
AU  - Evans S
AD  - Center for Cardiovascular Research, Cardiovascular Division and.
FAU - Tzeng, Huei-Ping
AU  - Tzeng HP
AD  - Center for Cardiovascular Research, Cardiovascular Division and.
FAU - Veis, Deborah J
AU  - Veis DJ
AD  - Division of Bone and Mineral Metabolism, Department of Medicine, Washington 
      University School of Medicine, St. Louis, Missouri, USA.
FAU - Matkovich, Scot
AU  - Matkovich S
AD  - Center for Cardiovascular Research, Cardiovascular Division and.
FAU - Weinheimer, Carla
AU  - Weinheimer C
AD  - Center for Cardiovascular Research, Cardiovascular Division and.
FAU - Kovacs, Attila
AU  - Kovacs A
AD  - Center for Cardiovascular Research, Cardiovascular Division and.
FAU - Barger, Philip M
AU  - Barger PM
AD  - Center for Cardiovascular Research, Cardiovascular Division and.
FAU - Mann, Douglas L
AU  - Mann DL
AD  - Center for Cardiovascular Research, Cardiovascular Division and.
LA  - eng
GR  - R01 AR070030/AR/NIAMS NIH HHS/United States
GR  - R01 HL058081/HL/NHLBI NIH HHS/United States
GR  - R01 HL089543/HL/NHLBI NIH HHS/United States
GR  - R01 HL111094/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20180208
PL  - United States
TA  - JCI Insight
JT  - JCI insight
JID - 101676073
RN  - 0 (Relb protein, mouse)
RN  - 0 (TNF Receptor-Associated Factor 2)
RN  - 0 (TRAF2 protein, mouse)
RN  - 147337-75-5 (Transcription Factor RelB)
SB  - IM
MH  - Animals
MH  - Humans
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Myocardial Infarction/etiology/*pathology
MH  - Signal Transduction/physiology
MH  - TNF Receptor-Associated Factor 2/genetics/*metabolism
MH  - Transcription Factor RelB/genetics/*metabolism
MH  - Ventricular Remodeling/*physiology
PMC - PMC5821173
OTO - NOTNLM
OT  - Cardiology
OT  - Innate immunity
COIS- Conflict of interest: The authors have declared that no conflict of interest 
      exists.
EDAT- 2018/02/09 06:00
MHDA- 2019/10/29 06:00
PMCR- 2018/02/08
CRDT- 2018/02/09 06:00
PHST- 2017/10/23 00:00 [received]
PHST- 2018/01/05 00:00 [accepted]
PHST- 2018/02/09 06:00 [pubmed]
PHST- 2019/10/29 06:00 [medline]
PHST- 2018/02/09 06:00 [entrez]
PHST- 2018/02/08 00:00 [pmc-release]
AID - 98278 [pii]
AID - 10.1172/jci.insight.98278 [doi]
PST - epublish
SO  - JCI Insight. 2018 Feb 8;3(3):e98278. doi: 10.1172/jci.insight.98278. eCollection 
      2018 Feb 8.