Integrin alpha-5 silencing leads to myofibroblastic differentiation in IPF-derived human lung fibroblasts

Autor: Gali Epstein Shochet, Elizabetha Brook, Becky Bardenstein-Wald, Hanna Grobe, Evgeny Edelstein, Lilach Israeli-Shani, David Shitrit
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Therapeutic Advances in Chronic Disease, Vol 11 (2020)
Druh dokumentu: article
ISSN: 2040-6231
20406223
DOI: 10.1177/2040622320936023
Popis: Background and objective: The term ‘fibroblast’ covers a heterogeneous cell population in idiopathic pulmonary fibrosis (IPF). The fibroblasts are considered as main effector cells, because they promote disease progression by releasing exaggerated amounts of extracellular matrix proteins and modifying cell microenvironment. As IPF-derived human lung fibroblasts (IPF-HLFs) were shown to express higher levels of integrin alpha-5 (ITGA5) than normal derived HLFs (N-HLFs), we explored the importance of ITGA5 to IPF progression. Methods: IPF-HLF and N-HLF primary cultures were established. ITGA5 was silenced by specific small interfering RNA (siRNA)s and its effects on cell phenotype (e.g. cell number, size, cell death, migration) and gene expression (e.g. RNA sequencing, quantitative polymerase chain reaction [qPCR], western blot and immunofluorescence) were tested. Specific integrin expression was evaluated in IPF patient formalin-fixed paraffin embedded sections by immunohistochemistry (IHC). Results: ITGA5-silencing resulted in reduced IPF-HLF proliferation rates and cell migration ( p
Databáze: Directory of Open Access Journals