PMID- 34438016
OWN - NLM
STAT- MEDLINE
DCOM- 20220331
LR  - 20220401
IS  - 1873-3913 (Electronic)
IS  - 0898-6568 (Linking)
VI  - 87
DP  - 2021 Nov
TI  - Backstage players of fibrosis: NOX4, mTOR, HDAC, and S1P; companions of TGF-beta.
PG  - 110123
LID - S0898-6568(21)00212-6 [pii]
LID - 10.1016/j.cellsig.2021.110123 [doi]
AB  - The fibrotic process could be easily defined as a pathological excess of 
      extracellular matrix deposition, leading to disruption of tissue architecture and 
      eventually loss of function; however, this process involves a complex network of 
      several signal transduction pathways. Virtually almost all organs could be 
      affected by fibrosis, the most affected are the liver, lung, skin, kidney, heart, 
      and eyes; in all of them, the transforming growth factor-beta (TGF-beta) has a 
      central role. The canonical and non-canonical signal pathways of TGF-beta impact the 
      fibrotic process at the cellular and molecular levels, inducing the 
      epithelial-mesenchymal transition (EMT) and the induction of profibrotic gene 
      expression with the consequent increase in proteins such as alpha-smooth actin 
      (alpha-SMA), fibronectin, collagen, and other extracellular matrix proteins. 
      Recently, it has been reported that some molecules that have not been typically 
      associated with the fibrotic process, such as nicotinamide adenine dinucleotide 
      phosphate (NADPH) oxidase 4 (NOX4), mammalian target of rapamycin (mTOR), histone 
      deacetylases (HDAC), and sphingosine-1 phosphate (S1P); are critical in its 
      development. In this review, we describe and discuss the role of these new 
      players of fibrosis and the convergence with TGF-beta signaling pathways, unveiling 
      new insights into the panorama of fibrosis that could be useful for future 
      therapeutic targets.
CI  - Copyright (c) 2021 Elsevier Inc. All rights reserved.
FAU - Jimenez-Uribe, Alexis Paulina
AU  - Jimenez-Uribe AP
AD  - Facultad de Quimica, Departamento de Biologia, Universidad Nacional Autonoma de 
      Mexico, CDMX 04510, Mexico.
FAU - Gomez-Sierra, Tania
AU  - Gomez-Sierra T
AD  - Facultad de Quimica, Departamento de Biologia, Universidad Nacional Autonoma de 
      Mexico, CDMX 04510, Mexico.
FAU - Aparicio-Trejo, Omar Emiliano
AU  - Aparicio-Trejo OE
AD  - Departamento de Fisiopatologia Cardio-Renal, Instituto Nacional de Cardiologia 
      "Ignacio Chavez", Mexico City 14080, Mexico.
FAU - Orozco-Ibarra, Marisol
AU  - Orozco-Ibarra M
AD  - Laboratorio de Neurobiologia Molecular y Celular, Instituto Nacional de 
      Neurologia y Neurocirugia, Manuel Velasco Suarez, Av. Insurgentes Sur # 3877, La 
      Fama, Alcaldia Tlalpan, CP 14269 Ciudad de Mexico, Mexico.
FAU - Pedraza-Chaverri, Jose
AU  - Pedraza-Chaverri J
AD  - Facultad de Quimica, Departamento de Biologia, Universidad Nacional Autonoma de 
      Mexico, CDMX 04510, Mexico. Electronic address: pedraza@unam.mx.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20210824
PL  - England
TA  - Cell Signal
JT  - Cellular signalling
JID - 8904683
RN  - 0 (Transforming Growth Factor beta)
RN  - 0 (Transforming Growth Factor beta1)
RN  - EC 1.6.3.- (NADPH Oxidase 4)
RN  - EC 1.6.3.- (NOX4 protein, human)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 3.5.1.98 (Histone Deacetylases)
RN  - NGZ37HRE42 (Sphingosine)
SB  - IM
MH  - Fibrosis
MH  - Friends
MH  - Histone Deacetylases
MH  - Humans
MH  - NADPH Oxidase 4
MH  - *Sphingosine/metabolism
MH  - TOR Serine-Threonine Kinases
MH  - *Transforming Growth Factor beta/metabolism
MH  - Transforming Growth Factor beta1/metabolism
OTO - NOTNLM
OT  - Fibrosis
OT  - Histone deacetylases (HDAC)
OT  - Mammalian target of rapamycin (mTOR)
OT  - NADPH oxidase 4 (NOX4)
OT  - Sphingosine-1 phosphate (S1P)
OT  - TGF-beta signaling pathways
OT  - Therapeutic targets
EDAT- 2021/08/27 06:00
MHDA- 2022/04/01 06:00
CRDT- 2021/08/26 20:15
PHST- 2021/07/22 00:00 [received]
PHST- 2021/08/19 00:00 [revised]
PHST- 2021/08/20 00:00 [accepted]
PHST- 2021/08/27 06:00 [pubmed]
PHST- 2022/04/01 06:00 [medline]
PHST- 2021/08/26 20:15 [entrez]
AID - S0898-6568(21)00212-6 [pii]
AID - 10.1016/j.cellsig.2021.110123 [doi]
PST - ppublish
SO  - Cell Signal. 2021 Nov;87:110123. doi: 10.1016/j.cellsig.2021.110123. Epub 2021 
      Aug 24.