PMID- 34212273
OWN - NLM
STAT- MEDLINE
DCOM- 20230808
LR  - 20230814
IS  - 1573-6822 (Electronic)
IS  - 0742-2091 (Linking)
VI  - 39
IP  - 3
DP  - 2023 Jun
TI  - Hirudin ameliorates diabetic nephropathy by inhibiting Gsdmd-mediated pyroptosis.
PG  - 573-589
LID - 10.1007/s10565-021-09622-z [doi]
AB  - Our group previously reported that hirudin ameliorated diabetic nephropathy (DN) 
      in streptozotocin (STZ)-injected rats, but the mechanism remained largely 
      unknown. Therefore, we further explored its possible mechanism. We subcutaneously 
      injected 5 U hirudin into STZ-induced WT mice or Gasdermin D (Gsdmd)(-/-) (KO) 
      mice daily for 12 weeks, respectively, and evaluated their kidney injury. Next, 
      glomerular endothelial cells (GECs), renal tubular epithelial cells (RTECs), and 
      bone-marrow-derived macrophages (BMDMs) were isolated from WT mice and treated 
      with hirudin in the presence of high glucose/lipopolysaccharides and ATP to 
      measure the release of interleukin-18 and interleukin-1beta. Kidney injury induced 
      by STZ injection was significantly ameliorated by hirudin through inhibiting 
      Gsdmd-mediated pyroptosis in the mice, not Caspase 1-mediated apoptosis. 
      Meanwhile, hirudin also suppressed pyroptosis in primary GECs, RTECs, and BMDMs 
      in vitro. Moreover, the deletion of Gsdmd reduced pyroptosis and kidney injury 
      both in vivo and in vitro. We also found that hirudin regulated the expression of 
      Gsdmd by inhibiting interferon regulatory factor 2 (Irf2). Hirudin ameliorated 
      Gsdmd-mediated pyroptosis by inhibiting irf2, leading to the improvement of 
      kidney injury. Therefore, hirudin might serve as a potential therapeutic strategy 
      to treat DN.
CI  - (c) 2021. The Author(s), under exclusive licence to Springer Nature B.V.
FAU - Han, Jiarui
AU  - Han J
AD  - Henan University of Chinese Medicine, No. 156 Jinshui Dong Road, Zhengdong New 
      District, Zhengzhou, 450046, Henan, China.
AD  - Department of Nephropathy, Henan Provincial Hospital of Traditional Chinese 
      Medicine, the Second Hospital Affiliated to Henan University of Chinese Medicine, 
      No. 2 Dongfeng Road, Jinshui District, Zhengzhou, 450002, Henan, China.
FAU - Zuo, Zhenkui
AU  - Zuo Z
AD  - Henan University of Chinese Medicine, No. 156 Jinshui Dong Road, Zhengdong New 
      District, Zhengzhou, 450046, Henan, China. zuozhenkui3524@163.com.
AD  - Henan Provincial Hospital of Traditional Chinese Medicine, the Second Hospital 
      Affiliated to Henan University of Chinese Medicine, No. 2 Dongfeng Road, Jinshui 
      District, Zhengzhou, 450002, Henan, China. zuozhenkui3524@163.com.
FAU - Shi, Xiujie
AU  - Shi X
AD  - Henan University of Chinese Medicine, No. 156 Jinshui Dong Road, Zhengdong New 
      District, Zhengzhou, 450046, Henan, China.
AD  - Department of Nephropathy, Henan Provincial Hospital of Traditional Chinese 
      Medicine, the Second Hospital Affiliated to Henan University of Chinese Medicine, 
      No. 2 Dongfeng Road, Jinshui District, Zhengzhou, 450002, Henan, China.
FAU - Zhang, Yage
AU  - Zhang Y
AD  - Henan University of Chinese Medicine, No. 156 Jinshui Dong Road, Zhengdong New 
      District, Zhengzhou, 450046, Henan, China.
AD  - Department of Nephropathy, Henan Provincial Hospital of Traditional Chinese 
      Medicine, the Second Hospital Affiliated to Henan University of Chinese Medicine, 
      No. 2 Dongfeng Road, Jinshui District, Zhengzhou, 450002, Henan, China.
FAU - Peng, Zining
AU  - Peng Z
AD  - Henan University of Chinese Medicine, No. 156 Jinshui Dong Road, Zhengdong New 
      District, Zhengzhou, 450046, Henan, China.
AD  - Department of Nephropathy, Henan Provincial Hospital of Traditional Chinese 
      Medicine, the Second Hospital Affiliated to Henan University of Chinese Medicine, 
      No. 2 Dongfeng Road, Jinshui District, Zhengzhou, 450002, Henan, China.
FAU - Xing, Yufeng
AU  - Xing Y
AD  - Henan University of Chinese Medicine, No. 156 Jinshui Dong Road, Zhengdong New 
      District, Zhengzhou, 450046, Henan, China.
AD  - Department of Nephropathy, Henan Provincial Hospital of Traditional Chinese 
      Medicine, the Second Hospital Affiliated to Henan University of Chinese Medicine, 
      No. 2 Dongfeng Road, Jinshui District, Zhengzhou, 450002, Henan, China.
FAU - Pang, Xinxin
AU  - Pang X
AD  - Henan University of Chinese Medicine, No. 156 Jinshui Dong Road, Zhengdong New 
      District, Zhengzhou, 450046, Henan, China. pangxinxin_006@sina.com.
AD  - Department of Nephropathy, Henan Provincial Hospital of Traditional Chinese 
      Medicine, the Second Hospital Affiliated to Henan University of Chinese Medicine, 
      No. 2 Dongfeng Road, Jinshui District, Zhengzhou, 450002, Henan, China. 
      pangxinxin_006@sina.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210702
PL  - Switzerland
TA  - Cell Biol Toxicol
JT  - Cell biology and toxicology
JID - 8506639
RN  - 0 (Hirudins)
SB  - IM
MH  - Rats
MH  - Mice
MH  - Animals
MH  - *Diabetic Nephropathies/drug therapy/metabolism
MH  - Hirudins/pharmacology/metabolism
MH  - Endothelial Cells/metabolism
MH  - Pyroptosis
MH  - Kidney
MH  - *Diabetes Mellitus/metabolism
OTO - NOTNLM
OT  - DN
OT  - Gsdmd
OT  - Hirudin
OT  - Irf2
OT  - Pyroptosis
EDAT- 2021/07/03 06:00
MHDA- 2023/08/08 06:42
CRDT- 2021/07/02 06:50
PHST- 2021/03/29 00:00 [received]
PHST- 2021/06/10 00:00 [accepted]
PHST- 2023/08/08 06:42 [medline]
PHST- 2021/07/03 06:00 [pubmed]
PHST- 2021/07/02 06:50 [entrez]
AID - 10.1007/s10565-021-09622-z [pii]
AID - 10.1007/s10565-021-09622-z [doi]
PST - ppublish
SO  - Cell Biol Toxicol. 2023 Jun;39(3):573-589. doi: 10.1007/s10565-021-09622-z. Epub 
      2021 Jul 2.