PMID- 37994436
OWN - NLM
STAT- MEDLINE
DCOM- 20231127
LR  - 20240410
IS  - 1525-6049 (Electronic)
IS  - 0886-022X (Print)
IS  - 0886-022X (Linking)
VI  - 45
IP  - 2
DP  - 2023
TI  - Astragalus polysaccharide promotes autophagy and alleviates diabetic nephropathy 
      by targeting the lncRNA Gm41268/PRLR pathway.
PG  - 2284211
LID - 10.1080/0886022X.2023.2284211 [doi]
LID - 2284211
AB  - BACKGROUND: Astragalus polysaccharide (APS) is a major bioactive component of the 
      Chinese herb astragalus, with well-established protective effects on the kidney. 
      However, the effect of APS on diabetic nephropathy (DN) is unclear. METHODS: Long 
      non-coding RNA (lncRNA) expression profiles in kidney samples from control, 
      db/db, and APS-treated db/db mice were evaluated using RNA high-throughput 
      sequencing techniques. Additionally, rat renal tubular epithelial (NRK-52E) cells 
      were cultured in high glucose (HG) media. We inhibited the expression of Gm41268 
      and prolactin receptor (PRLR) by transfecting NRK-52E cells with 
      Gm41268-targeting antisense oligonucleotides and PRLR siRNA. RESULTS: We found 
      that APS treatment reduced 24-h urinary protein levels and fasting blood glucose 
      and improved glucose intolerance and pathological renal damage in db/db mice. 
      Furthermore, APS treatment enhanced autophagy and alleviated fibrosis in the 
      db/db mice. We identified a novel lncRNA, Gm41268, which was differentially 
      expressed in the three groups, and the cis-regulatory target gene PRLR. APS 
      treatment induced autophagy by reducing p62 and p-mammalian target of rapamycin 
      (mTOR) protein levels and increasing the LC3 II/I ratio. Furthermore, APS 
      alleviated fibrosis by downregulating fibronectin (FN), transforming growth 
      factor-beta (TGF-beta), and collagen IV levels. In addition, APS reversed the 
      HG-induced overexpression of Gm41268 and PRLR. Reduction of Gm41268 decreased 
      PRLR expression, restored autophagy, and ameliorated renal fibrosis in vitro. 
      Inhibition of PRLR could enhance the protective effect of APS. CONCLUSIONS: In 
      summary, we demonstrated that the therapeutic effect of APS on DN is mediated via 
      the Gm41268/PRLR pathway. This information contributes to the exploration of 
      bioactive constituents in Chinese herbs as potential treatments for DN.
FAU - Chen, Zedong
AU  - Chen Z
AD  - School of Traditional Chinese Medicine, Jinan University, Guangzhou, China.
FAU - Liang, Huiyu
AU  - Liang H
AD  - School of Traditional Chinese Medicine, Jinan University, Guangzhou, China.
FAU - Yan, Xianxin
AU  - Yan X
AD  - School of Traditional Chinese Medicine, Jinan University, Guangzhou, China.
FAU - Liang, Qiuer
AU  - Liang Q
AD  - Affiliated Dongguan People's Hospital, Southern Medical University (Dongguan 
      People's Hospital), Guangzhou, China.
FAU - Bai, Zhenyu
AU  - Bai Z
AD  - School of Traditional Chinese Medicine, Jinan University, Guangzhou, China.
FAU - Xie, Ting
AU  - Xie T
AD  - School of Traditional Chinese Medicine, Jinan University, Guangzhou, China.
FAU - Dai, Jiaojiao
AU  - Dai J
AD  - School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 
      China.
FAU - Zhao, Xiaoshan
AU  - Zhao X
AD  - School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 
      China.
FAU - Xiao, Ya
AU  - Xiao Y
AD  - School of Traditional Chinese Medicine, Jinan University, Guangzhou, China.
LA  - eng
PT  - Journal Article
DEP - 20231123
PL  - England
TA  - Ren Fail
JT  - Renal failure
JID - 8701128
RN  - 0 (RNA, Long Noncoding)
RN  - 0 (Receptors, Prolactin)
RN  - 0 (Polysaccharides)
SB  - IM
MH  - Mice
MH  - Rats
MH  - Animals
MH  - *Diabetic Nephropathies/pathology
MH  - *RNA, Long Noncoding/genetics/metabolism
MH  - Receptors, Prolactin
MH  - Autophagy
MH  - Polysaccharides/pharmacology/therapeutic use
MH  - Fibrosis
MH  - Mammals/genetics/metabolism
MH  - *Diabetes Mellitus
PMC - PMC11001349
OTO - NOTNLM
OT  - Astragalus polysaccharide
OT  - LncRNA
OT  - autophagy
OT  - diabetic nephropathy
OT  - prolactin receptor
COIS- The authors declare no conflict of interest.
EDAT- 2023/11/23 06:42
MHDA- 2023/11/27 16:18
PMCR- 2023/11/23
CRDT- 2023/11/23 04:24
PHST- 2023/11/27 16:18 [medline]
PHST- 2023/11/23 06:42 [pubmed]
PHST- 2023/11/23 04:24 [entrez]
PHST- 2023/11/23 00:00 [pmc-release]
AID - 2284211 [pii]
AID - 10.1080/0886022X.2023.2284211 [doi]
PST - ppublish
SO  - Ren Fail. 2023;45(2):2284211. doi: 10.1080/0886022X.2023.2284211. Epub 2023 Nov 
      23.