PMID- 38280039
OWN - NLM
STAT- MEDLINE
DCOM- 20240129
LR  - 20240206
IS  - 1573-4978 (Electronic)
IS  - 0301-4851 (Print)
IS  - 0301-4851 (Linking)
VI  - 51
IP  - 1
DP  - 2024 Jan 27
TI  - Desmosterol-driven atypical macrophage polarization regulates podocyte dynamics 
      in diabetic nephropathy.
PG  - 213
LID - 10.1007/s11033-023-09198-3 [doi]
LID - 213
AB  - BACKGROUND: Diabetic nephropathy (DN) stands as a leading diabetes complication, 
      with macrophages intricately involved in its evolution. While glucose 
      metabolism's impact on macrophage activity is well-established, cholesterol 
      metabolism's contributions remain less explored. Our study seeks to elucidate 
      this association. METHODS AND RESULTS: Methods and Results: Gene expression 
      analysis of monocytes from the blood of both normal and diabetic patients was 
      conducted using public databases, showing that cholesterol metabolism pathways, 
      especially Bloch and Kandutsch-Russell, were more altered in diabetic 
      monocytes/macrophages than glucose-responsive pathways. When bone marrow-derived 
      macrophages (BMDMs) were subjected to desmosterol, they exhibited an 
      unconventional polarization. These BMDMs displayed heightened levels of both 
      M1-related pro-inflammatory cytokines and M2-linked anti-inflammatory factors. 
      Further, in co-culture, desmosterol-conditioned BMDMs paralleled M2 macrophages 
      in augmenting Ki-67 + podocyte populations while mimicking M1 macrophages in 
      elevating TUNEL + apoptotic podocytes. Comparable outcomes on podocytes were 
      obtained using conditioned media from the respective BMDMs. CONCLUSIONS: Our data 
      underscores the pivotal role of cholesterol metabolism, particularly via 
      desmosterol, in steering macrophages toward an unconventional polarization marked 
      by both inflammatory and regulatory traits. Such unique macrophage behavior 
      concurrently impacts podocyte proliferation and apoptosis, shedding fresh light 
      on DN pathogenesis and hinting at potential therapeutic interventions.
CI  - (c) 2024. The Author(s).
FAU - Qi, Huiying
AU  - Qi H
AD  - Department of Cardiology, Branch of Tianjin Third Central Hospital, 220 Jiangdu 
      Road, Tianjin, 300250, China. 13920699990@163.com.
LA  - eng
PT  - Journal Article
DEP - 20240127
PL  - Netherlands
TA  - Mol Biol Rep
JT  - Molecular biology reports
JID - 0403234
RN  - 313-04-2 (Desmosterol)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Humans
MH  - *Diabetic Nephropathies/metabolism
MH  - *Podocytes/metabolism
MH  - Desmosterol/metabolism
MH  - Macrophages/metabolism
MH  - Glucose/metabolism
MH  - *Diabetes Mellitus/metabolism
PMC - PMC10821991
OTO - NOTNLM
OT  - Desmosterol
OT  - Diabetic nephropathy
OT  - Macrophages
OT  - Podocytes
OT  - Polarization
COIS- The author has declared that no competing interests exist.
EDAT- 2024/01/28 07:42
MHDA- 2024/01/29 06:42
PMCR- 2024/01/27
CRDT- 2024/01/27 11:15
PHST- 2023/10/23 00:00 [received]
PHST- 2023/12/28 00:00 [accepted]
PHST- 2024/01/29 06:42 [medline]
PHST- 2024/01/28 07:42 [pubmed]
PHST- 2024/01/27 11:15 [entrez]
PHST- 2024/01/27 00:00 [pmc-release]
AID - 10.1007/s11033-023-09198-3 [pii]
AID - 9198 [pii]
AID - 10.1007/s11033-023-09198-3 [doi]
PST - epublish
SO  - Mol Biol Rep. 2024 Jan 27;51(1):213. doi: 10.1007/s11033-023-09198-3.