PMID- 34361079
OWN - NLM
STAT- MEDLINE
DCOM- 20210813
LR  - 20210813
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 22
IP  - 15
DP  - 2021 Aug 2
TI  - Liver-Specific Overexpression of Prostasin Attenuates High-Fat Diet-Induced 
      Metabolic Dysregulation in Mice.
LID - 10.3390/ijms22158314 [doi]
LID - 8314
AB  - The liver has a most indispensable role in glucose and lipid metabolism where we 
      see some of the most serious worldwide health problems. The serine protease 
      prostasin (PRSS8) cleaves toll-like receptor 4 (TLR4) and regulates hepatic 
      insulin sensitivity under PRSS8 knockout condition. However, liver substrate 
      proteins of PRSS8 other than TLR4 and the effect to glucose and lipid metabolism 
      remain unclarified with hepatic elevation of PRSS8 expression. Here we show that 
      high-fat-diet-fed liver-specific PRSS8 transgenic mice improved glucose tolerance 
      and hepatic steatosis independent of body weight. PRSS8 amplified extracellular 
      signal-regulated kinase phosphorylation associated with matrix metalloproteinase 
      14 activation in vivo and in vitro. Moreover, in humans, serum PRSS8 levels 
      reduced more in type 2 diabetes mellitus (T2DM) patients than healthy controls 
      and were lower in T2DM patients with increased maximum carotid artery intima 
      media thickness (>1.1 mm). These results identify the regulatory mechanisms of 
      PRSS8 overexpression over glucose and lipid metabolism, as well as excessive 
      hepatic fat storage.
FAU - Sekine, Tetsuo
AU  - Sekine T
AD  - Interdisciplinary Graduate School of Medicine and Engineering, University of 
      Yamanashi, Chuo 4093898, Japan.
FAU - Takizawa, Soichi
AU  - Takizawa S
AD  - Interdisciplinary Graduate School of Medicine and Engineering, University of 
      Yamanashi, Chuo 4093898, Japan.
AD  - Internal Medicine, Yamanashi Prefectural Central Hospital, Kofu 4008506, Japan.
FAU - Uchimura, Kohei
AU  - Uchimura K
AUID- ORCID: 0000-0003-2606-9762
AD  - Interdisciplinary Graduate School of Medicine and Engineering, University of 
      Yamanashi, Chuo 4093898, Japan.
FAU - Miyazaki, Asako
AU  - Miyazaki A
AD  - Isawa Hot Spring Hospital, Fuefuki 4060023, Japan.
FAU - Tsuchiya, Kyoichiro
AU  - Tsuchiya K
AD  - Interdisciplinary Graduate School of Medicine and Engineering, University of 
      Yamanashi, Chuo 4093898, Japan.
LA  - eng
GR  - 20K08883/Japan Society for the Promotion of Science/
PT  - Journal Article
DEP - 20210802
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - EC 3.4.21.- (Serine Endopeptidases)
RN  - EC 3.4.21.- (prostasin)
SB  - IM
MH  - Animals
MH  - Body Weight
MH  - Case-Control Studies
MH  - Diabetes Mellitus, Type 2/metabolism/*pathology
MH  - Diet, High-Fat/*adverse effects
MH  - Fatty Liver/etiology/metabolism/*pathology
MH  - Female
MH  - Lipid Metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Serine Endopeptidases/genetics/*metabolism
PMC - PMC8348244
OTO - NOTNLM
OT  - diabetes mellitus
OT  - extracellular signal-regulated MAP kinase
OT  - fatty liver
OT  - matrix metalloproteinase 14
OT  - serine protease
COIS- The authors declare no conflict of interest.
EDAT- 2021/08/08 06:00
MHDA- 2021/08/14 06:00
PMCR- 2021/08/02
CRDT- 2021/08/07 01:09
PHST- 2021/05/17 00:00 [received]
PHST- 2021/07/12 00:00 [revised]
PHST- 2021/07/30 00:00 [accepted]
PHST- 2021/08/07 01:09 [entrez]
PHST- 2021/08/08 06:00 [pubmed]
PHST- 2021/08/14 06:00 [medline]
PHST- 2021/08/02 00:00 [pmc-release]
AID - ijms22158314 [pii]
AID - ijms-22-08314 [pii]
AID - 10.3390/ijms22158314 [doi]
PST - epublish
SO  - Int J Mol Sci. 2021 Aug 2;22(15):8314. doi: 10.3390/ijms22158314.