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Ochratoxin A induced differentiation nephrotoxicity in renal tubule and glomeruli via autophagy differential regulation
Institution:1. Southeast University, Nanjing 211189, China;2. College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, Jiangsu, China;3. Engineering Research Center of Clinical Functional Materials and Diagnosis & Treatment Devices of Zhejiang Province, Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou 325001, China;1. School of Life Science, College of Environment and Resource, Shanxi University, Taiyuan 030006, China;2. Department of Biochemistry and Molecular Biology, Shanxi Key Laboratory of Birth Defect and Cell Regeneration, Shanxi Medical University, Taiyuan 030001, China;1. College of Ecological Technology and Engineering, Shanghai Institute of Technology, Shanghai 201418, PR China;2. Jiaxing Tongji Institute for Environment, Jiaxing, Zhejiang 314051, PR China;3. College of Environmental Science and Engineering, Tongji University, Shanghai 200092, PR China;1. Department of Occupational Health and Occupational Diseases, College of Public Health, Zhengzhou University, Zhengzhou 450001, Henan, China;2. The Key Laboratory of Nanomedicine and Health Inspection of Zhengzhou, Zhengzhou 450001, Henan, China;3. Biotherapy Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou 450052, Henan, China
Abstract:Ochratoxin A (OTA) is a mycotoxin that mainly causes nephrotoxicity. The single nephrotoxicity of OTA exposure on glomeruli or renal tubule had been well documented, however, the comparison toxicity between it is still unclear. Here, C57BL/6 mice and two types of nephrocyte were treated with concentration-gradient OTA to explore its differentiation nephrotoxicity. Results showed that OTA induced nephrotoxicity in vivo and in vitro, manifested as the deteriorative kidney function in mice and the cut-down cell viability in nephrocyte. Besides, results of murine kidney pathological section and IC50 of two types nephrocyte indicated that OTA-induced toxicity in renal tubule was higher than its in glomeruli. In addition, OTA exposure induced autophagy signaling differentiation expression. It revealed that autophagy was implicated in OTA-induced differential nephrotoxicity in glomeruli and renal tubule. Altogether, we proved that OTA induces a differentiation nephrotoxicity in glomeruli and renal tubule, and it is related to autophagy differential regulation.
Keywords:Ochratoxin A  Nephrotoxicity  Glomeruli  Renal tubules  Autophagy  OTA"}  {"#name":"keyword"  "$":{"id":"key0035"}  "$$":[{"#name":"text"  "_":"ochratoxin A  HGMC"}  {"#name":"keyword"  "$":{"id":"key0045"}  "$$":[{"#name":"text"  "_":"Human glomerular mesangial cell  HK-2 cells"}  {"#name":"keyword"  "$":{"id":"key0055"}  "$$":[{"#name":"text"  "_":"Human renal tubular epithelial cell  TGF-β"}  {"#name":"keyword"  "$":{"id":"key0065"}  "$$":[{"#name":"text"  "_":"transforming growth factor-beta  α-SMA"}  {"#name":"keyword"  "$":{"id":"key0075"}  "$$":[{"#name":"text"  "_":"alpha-smooth muscle actin  GFP-LC3"}  {"#name":"keyword"  "$":{"id":"key0085"}  "$$":[{"#name":"text"  "_":"green fluorescent protein-microtubule-associated protein 1 light-chain 3  3-MA"}  {"#name":"keyword"  "$":{"id":"key0095"}  "$$":[{"#name":"text"  "_":"3-Methyladenine  CQ"}  {"#name":"keyword"  "$":{"id":"key0105"}  "$$":[{"#name":"text"  "_":"chloroquine  AKT"}  {"#name":"keyword"  "$":{"id":"key0115"}  "$$":[{"#name":"text"  "_":"Protein kinase B  ATG5"}  {"#name":"keyword"  "$":{"id":"key0125"}  "$$":[{"#name":"text"  "_":"autophagy-related genes 5  ANOVA"}  {"#name":"keyword"  "$":{"id":"key0135"}  "$$":[{"#name":"text"  "_":"one-way analysis of variance  SD"}  {"#name":"keyword"  "$":{"id":"key0145"}  "$$":[{"#name":"text"  "_":"Standard Deviation  PI3K"}  {"#name":"keyword"  "$":{"id":"key0155"}  "$$":[{"#name":"text"  "_":"Phosphatidylinositol 3-kinase
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