PMID- 38154105
OWN - NLM
STAT- MEDLINE
DCOM- 20240129
LR  - 20240129
IS  - 1945-4589 (Electronic)
IS  - 1945-4589 (Linking)
VI  - 15
IP  - 24
DP  - 2023 Dec 27
TI  - Downregulating miR-184 relieves calcium oxalate crystal-mediated renal cell 
      damage via activating the Rap1 signaling pathway.
PG  - 14749-14763
LID - 10.18632/aging.205286 [doi]
AB  - BACKGROUND: Renal calculi are a very prevalent disease with a high incidence. 
      Calcium oxalate (CaOx) is a primary constituent of kidney stones. Our paper 
      probes the regulatory function and mechanism of miR-184 in CaOx-mediated renal 
      cell damage. METHODS: CaOx was used to treat HK2 cells and human podocytes (HPCs) 
      to simulate kidney cell damage. The qRT-PCR technique checked the profiles of 
      miR-184 and IGF1R. The examination of cell proliferation was conducted employing 
      CCK8. TUNEL staining was used to monitor cell apoptosis. Western blot analysis 
      was used to determine the protein profiles of apoptosis-concerned related 
      proteins (including Mcl1, Bcl-XL, and Caspase-3), the NF-kappaB, Nrf2/HO-1, and Rap1 
      signaling pathways. ELISA confirmed the levels of the inflammatory factors IL-6, 
      TNF-alpha, MCP1, and ICAM1. The targeting relationship between miR-184 and IGF1R was 
      validated by dual luciferase assay and RNA immunoprecipitation assay. RESULTS: 
      Glyoxylate-induced rat kidney stones model and HK2 and HPC cells treated with 
      CaOx demonstrated an increase in the miR-184 profile. Inhibiting miR-184 relieved 
      CaOx-mediated renal cell inflammation, apoptosis and oxidative stress and 
      activated the Rap1 pathway. IGF1R was targeted by miR-184. IGF1R activation by 
      IGF1 attenuated the effects of miR-184 on renal cell damage, and Hippo pathway 
      suppression reversed the inhibitory effect of miR-184 knockdown on renal cell 
      impairment. CONCLUSIONS: miR-184 downregulation activates the Rap1 signaling 
      pathway to ameliorate renal cell damage mediated by CaOx.
FAU - Han, Mei
AU  - Han M
AD  - Department of Emergency, The Fourth Hospital of Hebei Medical University, 
      Shijiazhuang 050000, China.
FAU - Zhang, Donghong
AU  - Zhang D
AD  - Department of Emergency, The Fourth Hospital of Hebei Medical University, 
      Shijiazhuang 050000, China.
FAU - Ji, Junwei
AU  - Ji J
AD  - Department of Emergency, The Fourth Hospital of Hebei Medical University, 
      Shijiazhuang 050000, China.
FAU - Zhang, Junli
AU  - Zhang J
AD  - Department of Emergency, The Second Hospital of Hebei Medical University, 
      Shijiazhuang 050000, China.
FAU - Qin, Mingyi
AU  - Qin M
AD  - Department of Nursing, The Fourth Hospital of Hebei Medical University, 
      Shijiazhuang 050000, China.
LA  - eng
PT  - Journal Article
DEP - 20231227
PL  - United States
TA  - Aging (Albany NY)
JT  - Aging
JID - 101508617
RN  - 2612HC57YE (Calcium Oxalate)
RN  - 0 (MicroRNAs)
RN  - 0 (MIRN184 microRNA, human)
RN  - 0 (MIRN184 microRNA, rat)
RN  - 0 (RAP1GAP protein, human)
SB  - IM
MH  - Animals
MH  - Humans
MH  - Rats
MH  - Calcium Oxalate/metabolism
MH  - Kidney/metabolism
MH  - *Kidney Calculi/genetics/metabolism
MH  - *MicroRNAs/genetics/metabolism
MH  - Signal Transduction
PMC - PMC10781483
OTO - NOTNLM
OT  - calcium oxalate crystal
OT  - inflammation
OT  - miR-484
OT  - renal injury
COIS- CONFLICTS OF INTEREST: The authors declare that they have no conflicts of 
      interest.
EDAT- 2023/12/28 18:42
MHDA- 2024/01/08 06:43
PMCR- 2023/12/31
CRDT- 2023/12/28 16:44
PHST- 2023/04/17 00:00 [received]
PHST- 2023/10/02 00:00 [accepted]
PHST- 2024/01/08 06:43 [medline]
PHST- 2023/12/28 18:42 [pubmed]
PHST- 2023/12/28 16:44 [entrez]
PHST- 2023/12/31 00:00 [pmc-release]
AID - 205286 [pii]
AID - 10.18632/aging.205286 [doi]
PST - ppublish
SO  - Aging (Albany NY). 2023 Dec 27;15(24):14749-14763. doi: 10.18632/aging.205286. 
      Epub 2023 Dec 27.