PMID- 35420971
OWN - NLM
STAT- MEDLINE
DCOM- 20220418
LR  - 20231213
IS  - 2165-5987 (Electronic)
IS  - 2165-5979 (Print)
IS  - 2165-5979 (Linking)
VI  - 13
IP  - 4
DP  - 2022 Apr
TI  - Sp1 transcription factor represses transcription of phosphatase and tensin 
      homolog to aggravate lung injury in mice with type 2 diabetes mellitus-pulmonary 
      tuberculosis.
PG  - 9928-9944
LID - 10.1080/21655979.2022.2062196 [doi]
AB  - Type 2 diabetes mellitus (T2DM) can enhance the risk of mycobacterium 
      tuberculosis (Mtb) infection and aggravate pulmonary tuberculosis (PTB). This 
      study intended to explore the function of phosphatase and tensin homolog (PTEN) 
      in T2DM-PTB and the molecules involved. Mice were treated with streptozotocin to 
      induce T2DM and then infected with Mtb. The mice with T2DM had increased weight, 
      blood glucose level, glucose intolerance and insulin resistance, and increased 
      susceptibility to PTB after Mtb infection. PTEN was significantly downregulated 
      in mice with T2DM-PTB and it had specific predictive value in patients. 
      Overexpression of PTEN improved mouse survival and reduced bacterial load, 
      inflammatory infiltration, cell apoptosis, and fibrosis in lung tissues. Sp1 
      transcription factor (SP1) was predicted and identified as an upstream regulator 
      of PTEN. SP1 suppressed PTEN transcription. Silencing of SP1 enhanced mouse 
      survival and alleviated the lung injury, and it promoted the M1 polarization of 
      macrophages in murine lung tissues. However, further downregulation of PTEN 
      increased protein kinase B (Akt) phosphorylation and blocked the alleviating 
      roles of SP1 silencing in T2DM-PTB. This study demonstrates that SP1 represses 
      PTEN transcription to promote lung injury in mice with T2DM-PTB through Akt 
      activation.
FAU - Zhao, Hongmei
AU  - Zhao H
AD  - Department of Tuberculosis, Shenyang Chest Hospital, Shenyang, Liaoning, China.
FAU - Shi, Lian
AU  - Shi L
AD  - Department of Tuberculosis, Shenyang Chest Hospital, Shenyang, Liaoning, China.
FAU - Wang, Xiaohong
AU  - Wang X
AD  - Department of Tuberculosis, Shenyang Chest Hospital, Shenyang, Liaoning, China.
FAU - Yu, Xiuli
AU  - Yu X
AD  - Department of Respiratory and Critical Care, Shenyang Chest Hospital, Shenyang, 
      Liaoning, China.
FAU - Wang, Danfeng
AU  - Wang D
AD  - Department of Tuberculosis, Shenyang Chest Hospital, Shenyang, Liaoning, China.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Bioengineered
JT  - Bioengineered
JID - 101581063
RN  - 0 (Sp1 Transcription Factor)
RN  - 0 (SP1 protein, human)
RN  - 0 (Tensins)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 3.1.3.67 (PTEN Phosphohydrolase)
RN  - EC 3.1.3.67 (PTEN protein, human)
RN  - EC 3.1.3.67 (Pten protein, mouse)
SB  - IM
MH  - Animals
MH  - *Diabetes Mellitus, Type 2/complications/genetics
MH  - Humans
MH  - *Lung Injury/genetics
MH  - Mice
MH  - PTEN Phosphohydrolase
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Sp1 Transcription Factor/genetics
MH  - Tensins
MH  - *Tuberculosis, Pulmonary/complications/genetics
PMC - PMC9162029
OTO - NOTNLM
OT  - Akt
OT  - PTEN
OT  - SP1
OT  - Type 2 diabetes mellitus
OT  - pulmonary tuberculosis
COIS- No potential conflict of interest was reported by the author(s).
EDAT- 2022/04/15 06:00
MHDA- 2022/04/19 06:00
PMCR- 2022/04/14
CRDT- 2022/04/14 17:12
PHST- 2022/04/14 17:12 [entrez]
PHST- 2022/04/15 06:00 [pubmed]
PHST- 2022/04/19 06:00 [medline]
PHST- 2022/04/14 00:00 [pmc-release]
AID - 2062196 [pii]
AID - 10.1080/21655979.2022.2062196 [doi]
PST - ppublish
SO  - Bioengineered. 2022 Apr;13(4):9928-9944. doi: 10.1080/21655979.2022.2062196.