Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0034069 (
pulmonary fibrosis
)
7,050
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Polyhexamethylene guanidine phosphate (PHMG-p), a member of the polymeric guanidine family, has strong antimicrobial activity and may increase the risk of inflammation-associated
pulmonary fibrosis
. However, the effect of PHMG-p on the barrier function of the bronchial epithelium is unknown. Epithelial barrier functioning is maintained by tight junctions (TJs); damage to these TJs is the major cause of epithelial barrier breakdown during lung inflammation. The present study showed that, in BEAS-2B human bronchial epithelial cells, exposure to PHMG-p reduced the number of TJs and the E-cadherin level and impaired the integrity of the F-actin architecture. Furthermore, exposure to PHMG-p stimulated the calcium-dependent protease calpain-1, which breaks down TJs. However, treatment with the calpain-1 inhibitor, ALLN, reversed the PHMG-p-mediated impairment of TJs and the F-actin architecture. Furthermore, exposure to PHMG-p increased the intracellular Ca
2+
level via P2X purinoreceptor 7 (
P2RX7
) and inhibition of
P2RX7
abolished the PHMG-p-induced calpain-1 activity and protein degradation and increased the intracellular Ca
2+
level. Although exposure to PHMG-p increased the extracellular ATP level, hydrolysis of extracellular ATP by apyrase did not influence its detrimental effect on bronchial epithelial cells. These results implicate the impairment of TJs and the F-actin architecture in the pathogenesis of pulmonary diseases.
...
PMID:Polyhexamethylene Guanidine Phosphate Damages Tight Junctions and the F-Actin Architecture by Activating Calpain-1 via the P2RX7/Ca
2+
Signaling Pathway. 3187 59
