PMID- 35563616
OWN - NLM
STAT- MEDLINE
DCOM- 20220517
LR  - 20220716
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 23
IP  - 9
DP  - 2022 May 7
TI  - The Protective Role of pVHL in Imiquimod-Induced Psoriasis-like Skin 
      Inflammation.
LID - 10.3390/ijms23095226 [doi]
LID - 5226
AB  - Psoriasis is a chronic inflammatory disease distinguished by an excessive 
      proliferation and abnormal differentiation of keratinocytes. Immune cells, such 
      as T lymphocytes and neutrophils, and inflammatory cytokines, such as Tumor 
      Necrosis Factor-alpha (TNF-alpha) and interleukin 17 (IL-17), are essential for 
      maintaining psoriatic lesions. Additionally, a hypoxic milieu present in the skin 
      promotes the expression of transcriptional factor hypoxia-inducible factor-1 
      alpha (HIF-1alpha). This protein regulates the expression of angiogenic and 
      glycolytic factors, such as vascular endothelial grown factor and lactate 
      dehydrogenase (LDH), both relevant in chronic inflammation. The von Hippel-Lindau 
      protein (pVHL) is a negative regulator of HIF-1alpha. Previously, we found that pVHL 
      was almost absent in the lesions of psoriasis patients; therefore, we 
      investigated the impact of rescue pVHL expression in lesional skin. We used the 
      imiquimod-induced psoriasis-like mouse model as an adenoviral vector that allowed 
      us to express pVHL in the skin. Our data show that, in lesional skin, pVHL 
      expression was reduced, whereas HIF-1alpha was increased. Remarkably, the retrieval 
      of pVHL prevented psoriatic lesions, diminishing erythema, scale, and epidermal 
      and vascular thickness. Furthermore, pVHL expression was capable of reducing 
      HIF-1alpha, LDH, TNF-alpha and immune cell infiltration (mainly IL-17(+) neutrophils). In 
      conclusion, our results demonstrate that pVHL has a protective role to play in 
      the pathophysiology of psoriasis.
FAU - Martinez-Torres, Isai
AU  - Martinez-Torres I
AD  - Departamento de Inmunologia, Escuela Nacional de Ciencias Biologicas del 
      Instituto Politecnico Nacional, Plan de Ayala y Prolongacion de Carpio, Col. 
      Santo Tomas, Alcaldia Miguel Hidalgo, Ciudad de Mexico C.P. 11340, Mexico.
FAU - Tepale-Segura, Araceli
AU  - Tepale-Segura A
AUID- ORCID: 0000-0002-6983-9416
AD  - Departamento de Inmunologia, Escuela Nacional de Ciencias Biologicas del 
      Instituto Politecnico Nacional, Plan de Ayala y Prolongacion de Carpio, Col. 
      Santo Tomas, Alcaldia Miguel Hidalgo, Ciudad de Mexico C.P. 11340, Mexico.
AD  - Unidad de Investigacion Medica en Inmunoquimica, Hospital de Especialidades, 
      Centro Medico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Avenida 
      Cuauhtemoc 330 Col. Doctores, Alcaldia Cuauhtemoc, Ciudad de Mexico C.P. 06720, 
      Mexico.
FAU - Castro-Escamilla, Octavio
AU  - Castro-Escamilla O
AUID- ORCID: 0000-0002-4061-4854
AD  - Unidad de Investigacion Medica en Inmunoquimica, Hospital de Especialidades, 
      Centro Medico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Avenida 
      Cuauhtemoc 330 Col. Doctores, Alcaldia Cuauhtemoc, Ciudad de Mexico C.P. 06720, 
      Mexico.
AD  - Unidad de Investigacion en Virologia y Cancer, Hospital Infantil De Mexico 
      Federico Gomez, Dr. Marquez 162. Col. Doctores, Alcaldia Cuauhtemoc, Ciudad de 
      Mexico C.P. 06720, Mexico.
FAU - Cancino-Diaz, Juan Carlos
AU  - Cancino-Diaz JC
AD  - Departamento de Microbiologia, Escuela Nacional de Ciencias Biologicas del 
      Instituto Politecnico Nacional, Plan de Ayala y Prolongacion de Carpio, Col. 
      Santo Tomas, Alcaldia Miguel Hidalgo, Ciudad de Mexico C.P. 11340, Mexico.
FAU - Rodriguez-Martinez, Sandra
AU  - Rodriguez-Martinez S
AD  - Departamento de Inmunologia, Escuela Nacional de Ciencias Biologicas del 
      Instituto Politecnico Nacional, Plan de Ayala y Prolongacion de Carpio, Col. 
      Santo Tomas, Alcaldia Miguel Hidalgo, Ciudad de Mexico C.P. 11340, Mexico.
FAU - Perez-Tapia, Sonia Mayra
AU  - Perez-Tapia SM
AD  - Unidad de Desarrollo e Invstigacion en Bioterapeuticos (UDIBI), Escuela Nacional 
      de Ciencias Biologicas, Instituto Politecnico Nacional, Ciudad de Mexico C.P. 
      11340, Mexico.
FAU - Bonifaz, Laura C
AU  - Bonifaz LC
AD  - Unidad de Investigacion Medica en Inmunoquimica, Hospital de Especialidades, 
      Centro Medico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Avenida 
      Cuauhtemoc 330 Col. Doctores, Alcaldia Cuauhtemoc, Ciudad de Mexico C.P. 06720, 
      Mexico.
AD  - Coordinacion de Investigacion en Salud, Centro Medico Nacional Siglo XXI, 
      Instituto Mexicano del Seguro Social, Avenida Cuauhtemoc 330 Col. Doctores, 
      Alcaldia Cuauhtemoc, Ciudad de Mexico C.P. 06720, Mexico.
FAU - Cancino-Diaz, Mario Eugenio
AU  - Cancino-Diaz ME
AUID- ORCID: 0000-0003-0271-7892
AD  - Departamento de Inmunologia, Escuela Nacional de Ciencias Biologicas del 
      Instituto Politecnico Nacional, Plan de Ayala y Prolongacion de Carpio, Col. 
      Santo Tomas, Alcaldia Miguel Hidalgo, Ciudad de Mexico C.P. 11340, Mexico.
LA  - eng
GR  - SIP-20210140/Instituto Politecnico Nacional/
PT  - Journal Article
DEP - 20220507
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Interleukin-17)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 2.3.2.27 (Von Hippel-Lindau Tumor Suppressor Protein)
RN  - P1QW714R7M (Imiquimod)
SB  - IM
MH  - Animals
MH  - *Dermatitis
MH  - Humans
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/genetics
MH  - Imiquimod/adverse effects
MH  - Inflammation
MH  - Interleukin-17/genetics
MH  - Mice
MH  - *Psoriasis/chemically induced/drug therapy
MH  - Tumor Necrosis Factor-alpha/genetics
MH  - Von Hippel-Lindau Tumor Suppressor Protein/metabolism
PMC - PMC9104378
OTO - NOTNLM
OT  - IL-17
OT  - angiogenesis
OT  - hypoxia-inducible factor-1alpha (HIF-1alpha)
OT  - neutrophils
OT  - psoriasis
OT  - von Hippel-Lindau protein (pVHL)
COIS- The authors declare no conflict of interest.
EDAT- 2022/05/15 06:00
MHDA- 2022/05/18 06:00
PMCR- 2022/05/07
CRDT- 2022/05/14 01:07
PHST- 2022/02/28 00:00 [received]
PHST- 2022/04/29 00:00 [revised]
PHST- 2022/05/04 00:00 [accepted]
PHST- 2022/05/14 01:07 [entrez]
PHST- 2022/05/15 06:00 [pubmed]
PHST- 2022/05/18 06:00 [medline]
PHST- 2022/05/07 00:00 [pmc-release]
AID - ijms23095226 [pii]
AID - ijms-23-05226 [pii]
AID - 10.3390/ijms23095226 [doi]
PST - epublish
SO  - Int J Mol Sci. 2022 May 7;23(9):5226. doi: 10.3390/ijms23095226.