PMID- 37855350
OWN - NLM
STAT- Publisher
LR  - 20231019
IS  - 2212-3873 (Electronic)
IS  - 1871-5303 (Linking)
DP  - 2023 Oct 19
TI  - GDF15 Interference Regulates Proliferation, Inflammation, and Autophagy of 
      Lipopolysaccharide-induced Mesangial Cells by Inhibiting PI3K/ AKT/mTOR 
      Signaling.
LID - 10.2174/0118715303252127230926002355 [doi]
AB  - BACKGROUND: Chronic glomerulonephritis (CGN) is a primary glomerular disease. As 
      a circulating protein, growth and differentiation factor 15 (GDF15) participates 
      in a variety of biological processes. OBJECTIVE: We aimed to investigate the role 
      of GDF15 in CGN. METHODS: HBZY-1 cells were induced by lipopolysaccharide (LPS). 
      Cell viability was detected using a cell counting kit-8 (CCK-8) assay, and a 
      western blot was applied for the detection of GDF15 protein expression. After 
      GDF15 silencing, cell proliferation was evaluated by CCK-8 assay and 
      5-ethynyl-2'-deoxyuridine (EDU) staining. Enzyme-linked immunosorbent assay 
      (ELISA) kits were used to detect the levels of inflammatory cytokines. Autophagy 
      was assessed by GFP-LC3B assay. Besides, the expression of NF-kappaB signaling-, 
      autophagy- (LC3II/I, Beclin l and p62) and phosphoinositide 3-kinase 
      (PI3K)/protein kinase B (AKT)/mechanistic target of rapamycin (mTOR) 
      signaling-related proteins were measured by western blot. Afterwards, PI3K 
      agonist 740Y-P was used to clarify whether GDF15 affected LPS-induced HBZY-1 
      cells via PI3K/AKT/mTOR signaling. RESULTS: LPS induction increased cell 
      viability and elevated GDF15 expression in HBZY-1 cells. After GDF15 expression 
      depletion, the increased proliferation of LPS-induced HBZY-1 cells was decreased. 
      Additionally, GDF15 knockdown suppressed the release of inflammatory factors in 
      LPS-induced HBZY-1 cells and activated autophagy. Moreover, the PI3K/AKT/ mTOR 
      signal was evidenced to be activated by GDF15 deficiency. The further addition of 
      740Y-P reversed the impacts of GDF15 deficiency on the proliferation, 
      inflammation, and autophagy of LPS-induced HBZY-1 Conclusion: Collectively, GDF15 
      downregulation could protect against CGN via blocking PI3K/AKT/mTOR signaling.
CI  - Copyright(c) Bentham Science Publishers; For any queries, please email at 
      epub@benthamscience.net.
FAU - Chen, Zhen
AU  - Chen Z
AD  - Department of Nephrology, Shen Zhen Qianhai Shekou Free Trade Zone Hospital, 
      Shenzhen, 518067, China.
FAU - Gao, Liping
AU  - Gao L
AD  - Department of Nephrology, Shen Zhen Qianhai Shekou Free Trade Zone Hospital, 
      Shenzhen, 518067, China.
FAU - Li, Cailing
AU  - Li C
AD  - Department of Nephrology, Shen Zhen Qianhai Shekou Free Trade Zone Hospital, 
      Shenzhen, 518067, China.
FAU - Sun, Wenzhu
AU  - Sun W
AD  - Department of Nephrology, Shen Zhen Qianhai Shekou Free Trade Zone Hospital, 
      Shenzhen, 518067, China.
LA  - eng
PT  - Journal Article
DEP - 20231019
PL  - United Arab Emirates
TA  - Endocr Metab Immune Disord Drug Targets
JT  - Endocrine, metabolic & immune disorders drug targets
JID - 101269157
SB  - IM
OTO - NOTNLM
OT  - Chronic glomerulonephritis
OT  - GDF15
OT  - PI3K/AKT/mTOR signaling
OT  - autophagy
OT  - proliferation
EDAT- 2023/10/19 12:46
MHDA- 2023/10/19 12:46
CRDT- 2023/10/19 07:44
PHST- 2023/03/07 00:00 [received]
PHST- 2023/08/02 00:00 [revised]
PHST- 2023/08/31 00:00 [accepted]
PHST- 2023/10/19 12:46 [medline]
PHST- 2023/10/19 12:46 [pubmed]
PHST- 2023/10/19 07:44 [entrez]
AID - EMIDDT-EPUB-135359 [pii]
AID - 10.2174/0118715303252127230926002355 [doi]
PST - aheadofprint
SO  - Endocr Metab Immune Disord Drug Targets. 2023 Oct 19. doi: 
      10.2174/0118715303252127230926002355.