The laminin-binding integrins regulate nuclear factor κB-dependent epithelial cell polarity and inflammation.
Cytokines
Epithelial-to-mesenchymal transition
Fibrosis
Inflammation
Journal
Journal of cell science
ISSN: 1477-9137
Titre abrégé: J Cell Sci
Pays: England
ID NLM: 0052457
Informations de publication
Date de publication:
15 12 2021
15 12 2021
Historique:
received:
18
07
2021
accepted:
18
11
2021
pubmed:
30
11
2021
medline:
3
2
2022
entrez:
29
11
2021
Statut:
ppublish
Résumé
The main laminin-binding integrins α3β1, α6β1 and α6β4 are co-expressed in the developing kidney collecting duct system. We previously showed that deleting the integrin α3 or α6 subunit in the ureteric bud, which gives rise to the kidney collecting system, caused either a mild or no branching morphogenesis phenotype, respectively. To determine whether these two integrin subunits cooperate in kidney collecting duct development, we deleted α3 and α6 in the developing ureteric bud. The collecting system of the double knockout phenocopied the α3 integrin conditional knockout. However, with age, the mice developed severe inflammation and fibrosis around the collecting ducts, resulting in kidney failure. Integrin α3α6-null collecting duct epithelial cells showed increased secretion of pro-inflammatory cytokines and displayed mesenchymal characteristics, causing loss of barrier function. These features resulted from increased nuclear factor kappa-B (NF-κB) activity, which regulated the Snail and Slug (also known as Snai1 and Snai2, respectively) transcription factors and their downstream targets. These data suggest that laminin-binding integrins play a key role in the maintenance of kidney tubule epithelial cell polarity and decrease pro-inflammatory cytokine secretion by regulating NF-κB-dependent signaling.
Identifiants
pubmed: 34841431
pii: 273835
doi: 10.1242/jcs.259161
pmc: PMC8729780
pii:
doi:
Substances chimiques
Integrin alpha3beta1
0
Integrins
0
Laminin
0
NF-kappa B
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK069921
Pays : United States
Organisme : NIDDK NIH HHS
ID : T32 DK007569
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK119212
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK127589
Pays : United States
Organisme : BLRD VA
ID : I01 BX003425
Pays : United States
Organisme : NHLBI NIH HHS
ID : R03 HL154287
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL151016
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK114809
Pays : United States
Organisme : BLRD VA
ID : IK6 BX005240
Pays : United States
Organisme : BLRD VA
ID : I01 BX002196
Pays : United States
Organisme : NIH HHS
ID : R01 DK069921
Pays : United States
Organisme : NIH HHS
ID : P30-DK-114809
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK108968
Pays : United States
Organisme : NHLBI NIH HHS
ID : K08 HL127102
Pays : United States
Organisme : BLRD VA
ID : I01 BX002025
Pays : United States
Informations de copyright
© 2021. Published by The Company of Biologists Ltd.
Déclaration de conflit d'intérêts
Competing interests The authors declare no competing or financial interests.
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