Granulin in renal tubular epithelia is associated with interstitial inflammation and activates the TLR9-IFN-α pathway in lupus nephritis.
Lupus
; 33(5): 439-449, 2024 Apr.
Article
en En
| MEDLINE
| ID: mdl-38334360
ABSTRACT
OBJECTIVE:
This study aimed to investigate the possible role of granulin (GRN) in activating the TLR9-IFN-α pathway in renal tubular epithelial cells (RTECs) and explore clues that RTECs regulate the micro-environment of inflammatory response in lupus nephritis (LN).METHODS:
Renal sections from 57 LN patients and 30 non-LN patients were sampled for histological study, and GRN overexpression RTECs were applied for cytological study.RESULTS:
In the histological study, GRN is highly expressed in LN RTECs with tubulointerstitial inflammation (TII) and well co-localized with TLR9. ROC analysis suggested a potential relationship between GRN expression in RTECs and therapeutic response. Moreover, IFN-α also highly expressed in LN RTECs with TII, and the intensity of IFN-α is positively correlated with the co-localization intensity of GRN and TLR9. In the cytological study, LN serum, especially serum from LN with TII, activates the expression of TLR9 in RTECs, and GRN engages the interaction of TLR9 to activate the expression of IFN-α in RTECs. While TLR9 inhibitors can suppress the expression of IFN-α in RTECs, the degree of inhibition is dose-dependent.CONCLUSION:
The expression of GRN in RTECs is associated with interstitial inflammation and therapeutic response. GRN may mediate the activation of the TLR9-IFN-α pathway in RTECs and involve in the micro-environment of inflammatory response in LN.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Nefritis Lúpica
/
Granulinas
/
Lupus Eritematoso Sistémico
Tipo de estudio:
Risk_factors_studies
Límite:
Humans
Idioma:
En
Revista:
Lupus
Asunto de la revista:
REUMATOLOGIA
Año:
2024
Tipo del documento:
Article
País de afiliación:
China