PMID- 30535458
OWN - NLM
STAT- MEDLINE
DCOM- 20190528
LR  - 20211204
IS  - 1791-3004 (Electronic)
IS  - 1791-2997 (Linking)
VI  - 19
IP  - 2
DP  - 2019 Feb
TI  - Role of the mTOR‑FOXO1 pathway in obesity‑associated renal tubulointerstitial 
      inflammation.
PG  - 1284-1293
LID - 10.3892/mmr.2018.9727 [doi]
AB  - Since obesity is largely responsible for the growing incidence of renal 
      tubulointerstitial inflammation, exploration into the mechanisms of 
      obesity‑associated tubulointerstitial inflammation is essential. Studies have 
      demonstrated that mammalian target of rapamycin (mTOR) is a crucial molecule in 
      the pathogenesis of renal inflammation, including regulating the expression of 
      inflammatory factors. The purpose of the present study was to further elucidate 
      the role of mTOR in obesity‑associated tubulointerstitial inflammation. In the 
      clinical study, obese and healthy subjects were recruited for physical 
      examination, as well as the collection of blood and urine samples. Further study 
      was performed on a high fat diet (HFD)‑induced obese rat model and a cultured 
      human renal tubular epithelial cell line (HK‑2). The clinical study demonstrated 
      that the participants with obesity had increased serum lipids, creatinine (Cr), 
      urinary albumin to creatinine ratio (UACR) and urinary neutrophil 
      gelatinase‑associated lipocalin (u‑NGAL). Moreover, the level of urinary monocyte 
      chemoattractant protein‑1 (u‑MCP‑1) was increased in the participants with 
      obesity, and it was positively correlated with free fatty acid (FFA), UACR and 
      u‑NGAL. In the in vivo study, the results indicated that the levels of serum 
      lipids, Cr and blood urea nitrogen (BUN), as well as 24 h urine protein and 
      u‑NGAL, were signi fi cantly increased in the HFD‑fed obese rats. In addition, the 
      infiltration of CD68+ cells into the renal interstitial area and the release of 
      interleukin‑1beta (IL‑1beta) was observed in the kidneys of obese rats. Meanwhile, the 
      supernatant from HK‑2 cells treated with palmitic acid stimulated THP‑1 monocyte 
      migration. The upregulation of MCP‑1, phosphorylated forkhead boxO1 (p‑FOXO1), 
      and phosphorylated mTOR (p‑mTOR) was observed in vivo and in vitro. However, 
      inhibition of mTOR was able to alleviate the above effects. Overall, these 
      results demonstrated that activated mTOR induced FOXO1 phosphorylation, which 
      mediates renal MCP‑1 release, causes tubulointerstitial inflammation and 
      ultimately leads to pathological renal changes and dysfunction. However, 
      inhibition of mTOR may play a renoprotective role during the progression of 
      obesity‑associated tubulointerstitial inflammation.
FAU - Sun, Hong
AU  - Sun H
AD  - Department of Endocrinology and Metabolism, The First Affiliated Hospital of 
      Soochow University, Suzhou, Jiangsu 215006, P.R. China.
FAU - Shao, Xinyu
AU  - Shao X
AD  - Department of Endocrinology and Metabolism, The First Affiliated Hospital of 
      Soochow University, Suzhou, Jiangsu 215006, P.R. China.
FAU - He, Jiajia
AU  - He J
AD  - Department of Oncology, The Third Affiliated Hospital of Soochow University, The 
      First People's Hospital of Changzhou, Changzhou, Jiangsu 213000, P.R. China.
FAU - Golos, Michal
AU  - Golos M
AD  - Centre for Amyloidosis and Acute Phase Protein, Division of Medicine, University 
      College London (UCL), London NW3 2PF, UK.
FAU - Shi, Bimin
AU  - Shi B
AD  - Department of Endocrinology and Metabolism, The First Affiliated Hospital of 
      Soochow University, Suzhou, Jiangsu 215006, P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20181205
PL  - Greece
TA  - Mol Med Rep
JT  - Molecular medicine reports
JID - 101475259
RN  - 0 (Antigens, CD)
RN  - 0 (Antigens, Differentiation, Myelomonocytic)
RN  - 0 (CD68 antigen, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (FOXO1 protein, human)
RN  - 0 (Forkhead Box Protein O1)
RN  - 0 (Interleukin-1beta)
RN  - 0 (Lipocalin-2)
RN  - AYI8EX34EU (Creatinine)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Adult
MH  - Animals
MH  - Antigens, CD/metabolism
MH  - Antigens, Differentiation, Myelomonocytic/metabolism
MH  - Cell Line
MH  - Chemokine CCL2/metabolism
MH  - Creatinine/blood
MH  - Diet, High-Fat/adverse effects
MH  - Epithelial Cells/metabolism
MH  - Female
MH  - Forkhead Box Protein O1/*metabolism
MH  - Humans
MH  - Inflammation/*metabolism
MH  - Interleukin-1beta/metabolism
MH  - Kidney/*metabolism
MH  - Lipocalin-2/metabolism
MH  - Male
MH  - Nephritis, Interstitial/*metabolism
MH  - Obesity/*metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - TOR Serine-Threonine Kinases/*metabolism
OTO - NOTNLM
OT  - obesity
OT  - renal tubulointerstitial inflammation
OT  - monocyte chemoattractant protein‑1
OT  - forkhead boxO1
OT  - mammalian target of rapamycin
EDAT- 2018/12/12 06:00
MHDA- 2019/05/29 06:00
CRDT- 2018/12/12 06:00
PHST- 2018/08/05 00:00 [received]
PHST- 2018/11/13 00:00 [accepted]
PHST- 2018/12/12 06:00 [pubmed]
PHST- 2019/05/29 06:00 [medline]
PHST- 2018/12/12 06:00 [entrez]
AID - 10.3892/mmr.2018.9727 [doi]
PST - ppublish
SO  - Mol Med Rep. 2019 Feb;19(2):1284-1293. doi: 10.3892/mmr.2018.9727. Epub 2018 Dec 
      5.