PMID- 31390845
OWN - NLM
STAT- MEDLINE
DCOM- 20200622
LR  - 20200622
IS  - 2218-273X (Electronic)
IS  - 2218-273X (Linking)
VI  - 9
IP  - 8
DP  - 2019 Aug 6
TI  - Microparticles as Potential Mediators of High Glucose-Induced Renal Cell Injury.
LID - 10.3390/biom9080348 [doi]
LID - 348
AB  - Diabetic nephropathy (DN) is the most common cause of chronic kidney disease 
      worldwide. Activation of signaling pathways such as the mammalian target of 
      rapamycin (mTOR), extracellular signal-regulated kinases (ERK), endoplasmic 
      reticulum (ER) stress, transforming growth factor-beta (TGF-beta), and 
      epithelial-mesenchymal transition (EMT), are thought to play a significant role 
      in the etiology of DN. Microparticles (MPs), the small membrane vesicles 
      containing bioactive signals shed by cells upon activation or during apoptosis, 
      are elevated in diabetes and were identified as biomarkers in DN. However, their 
      exact role in the pathophysiology of DN remains unclear. Here, we examined the 
      effect of MPs shed from renal proximal tubular cells (RPTCs) exposed to high 
      glucose conditions on naive RPTCs in vitro. Our results showed significant 
      increases in the levels of phosphorylated forms of 4E-binding protein 1 and 
      ERK1/2 (the downstream targets of mTOR and ERK pathways), phosphorylated-eIF2alpha 
      (an ER stress marker), alpha smooth muscle actin (an EMT marker), and 
      phosphorylated-SMAD2 and nuclear translocation of SMAD4 (markers of TGF-beta 
      signaling). Together, our findings indicate that MPs activate key signaling 
      pathways in RPTCs under high glucose conditions. Pharmacological interventions to 
      inhibit shedding of MPs from RPTCs might serve as an effective strategy to 
      prevent the progression of DN.
FAU - Ravindran, Sreenithya
AU  - Ravindran S
AD  - Department of Pharmaceutical Sciences, College of Pharmacy, QU Health, Qatar 
      University, P.O Box 2713, Doha, Qatar.
FAU - Pasha, Mazhar
AU  - Pasha M
AD  - Department of Pharmaceutical Sciences, College of Pharmacy, QU Health, Qatar 
      University, P.O Box 2713, Doha, Qatar.
FAU - Agouni, Abdelali
AU  - Agouni A
AD  - Department of Pharmaceutical Sciences, College of Pharmacy, QU Health, Qatar 
      University, P.O Box 2713, Doha, Qatar.
FAU - Munusamy, Shankar
AU  - Munusamy S
AD  - Department of Pharmaceutical and Administrative Sciences, College of Pharmacy and 
      Health Sciences, Drake University, Des Moines, IA 50311, USA. 
      shankar.munusamy@drake.edu.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190806
PL  - Switzerland
TA  - Biomolecules
JT  - Biomolecules
JID - 101596414
RN  - 0 (Microplastics)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Animals
MH  - Cell Cycle/drug effects
MH  - Cell Survival/drug effects
MH  - Cells, Cultured
MH  - Dose-Response Relationship, Drug
MH  - Glucose/chemistry/*pharmacology
MH  - Kidney Tubules, Proximal/*drug effects/metabolism/pathology
MH  - Microplastics/*chemistry
MH  - Rats
PMC - PMC6723350
OTO - NOTNLM
OT  - ERK1/2
OT  - TGF-beta
OT  - diabetic nephropathy
OT  - endoplasmic reticulum stress
OT  - epithelial-mesenchymal transition
OT  - mTOR
OT  - microparticles
COIS- The authors declare no conflict of interest.
EDAT- 2019/08/09 06:00
MHDA- 2020/06/23 06:00
PMCR- 2019/08/01
CRDT- 2019/08/09 06:00
PHST- 2019/06/27 00:00 [received]
PHST- 2019/07/31 00:00 [revised]
PHST- 2019/08/04 00:00 [accepted]
PHST- 2019/08/09 06:00 [entrez]
PHST- 2019/08/09 06:00 [pubmed]
PHST- 2020/06/23 06:00 [medline]
PHST- 2019/08/01 00:00 [pmc-release]
AID - biom9080348 [pii]
AID - biomolecules-09-00348 [pii]
AID - 10.3390/biom9080348 [doi]
PST - epublish
SO  - Biomolecules. 2019 Aug 6;9(8):348. doi: 10.3390/biom9080348.