PMID- 35455432
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220716
IS  - 1424-8247 (Print)
IS  - 1424-8247 (Electronic)
IS  - 1424-8247 (Linking)
VI  - 15
IP  - 4
DP  - 2022 Mar 31
TI  - ZLN005 Alleviates In Vivo and In Vitro Renal Fibrosis via PGC-1alpha-Mediated 
      Mitochondrial Homeostasis.
LID - 10.3390/ph15040434 [doi]
LID - 434
AB  - Currently, chronic kidney disease (CKD) is one of the most common diseases; it is 
      also a serious threat to human health due to its high mortality, and its 
      treatment is still a major clinical challenge. Mitochondrial dyshomeostasis plays 
      an important role in the development of CKD. ZLN005 is a novel 
      peroxisome-proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha) activator 
      from our laboratory. To explore whether ZLN005 can protect against CKD in vivo 
      and in vitro, a unilateral ureteral obstruction (UUO) model and TGF-beta1-treated 
      renal tubular epithelial cells (TECs), respectively, were used in this study. We 
      found that ZLN005-administrated UUO mice showed less kidney damages than control 
      mice, as indicated by the reduced expression of fibrotic biomarkers in the kidney 
      of UUO mice. ZLN005 treatment also alleviated the TGF-beta1-induced fibrotic 
      phenotype and lipid accumulation in TECs. Our study demonstrated ZLN005 treatment 
      improved mitochondrial homeostasis at least partially via the activation of 
      PGC-1alpha, thus maintaining mitochondria function and energy homeostasis. In 
      summary, ZLN005 treatment ameliorates UUO-induced renal fibrosis, providing 
      conceptional support for mitochondria-targeting therapies for chronic kidney 
      disease.
FAU - Zhu, Pengfei
AU  - Zhu P
AD  - The First Clinical Medical School, Nanjing University of Chinese Medicine, 
      Nanjing 210000, China.
AD  - State Key Laboratory of Drug Research, The National Center for Drug Screening, 
      Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 
      201203, China.
AD  - Department of Endocrinology, Jiangsu Province Hospital of Chinese Medicine, 
      Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210000, 
      China.
FAU - Ma, Haijian
AU  - Ma H
AD  - State Key Laboratory of Drug Research, The National Center for Drug Screening, 
      Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 
      201203, China.
FAU - Cui, Shichao
AU  - Cui S
AUID- ORCID: 0000-0002-8604-1270
AD  - State Key Laboratory of Drug Research, The National Center for Drug Screening, 
      Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 
      201203, China.
FAU - Zhou, Xiqiao
AU  - Zhou X
AD  - Department of Endocrinology, Jiangsu Province Hospital of Chinese Medicine, 
      Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210000, 
      China.
FAU - Xu, Weilong
AU  - Xu W
AD  - Department of Endocrinology, Jiangsu Province Hospital of Chinese Medicine, 
      Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210000, 
      China.
FAU - Yu, Jiangyi
AU  - Yu J
AD  - The First Clinical Medical School, Nanjing University of Chinese Medicine, 
      Nanjing 210000, China.
AD  - Department of Endocrinology, Jiangsu Province Hospital of Chinese Medicine, 
      Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210000, 
      China.
FAU - Li, Jingya
AU  - Li J
AD  - State Key Laboratory of Drug Research, The National Center for Drug Screening, 
      Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 
      201203, China.
AD  - School of Pharmaceutical Science and Technology, Hangzhou Institute for Advanced 
      Study, University of Chinese Academy of Sciences, Hangzhou 310000, China.
LA  - eng
GR  - 21S11907600 and 19431908100/Shanghai Commission of Science and Technology/
PT  - Journal Article
DEP - 20220331
PL  - Switzerland
TA  - Pharmaceuticals (Basel)
JT  - Pharmaceuticals (Basel, Switzerland)
JID - 101238453
PMC - PMC9025854
OTO - NOTNLM
OT  - PGC-1alpha
OT  - UUO
OT  - ZLN005
OT  - mitochondrial homeostasis
COIS- The authors declare no conflict of interest.
EDAT- 2022/04/24 06:00
MHDA- 2022/04/24 06:01
PMCR- 2022/03/31
CRDT- 2022/04/23 01:06
PHST- 2022/02/22 00:00 [received]
PHST- 2022/03/27 00:00 [revised]
PHST- 2022/03/29 00:00 [accepted]
PHST- 2022/04/23 01:06 [entrez]
PHST- 2022/04/24 06:00 [pubmed]
PHST- 2022/04/24 06:01 [medline]
PHST- 2022/03/31 00:00 [pmc-release]
AID - ph15040434 [pii]
AID - pharmaceuticals-15-00434 [pii]
AID - 10.3390/ph15040434 [doi]
PST - epublish
SO  - Pharmaceuticals (Basel). 2022 Mar 31;15(4):434. doi: 10.3390/ph15040434.