BACKGROUNDIdiopathic pulmonary fibrosis (IPF) is a progressive and lethal fibrotic lung disease of unknown etiology. Host susceptibility or genetic factors may be important for the predisposition to it. Transforming growth factor-β1 (TGF-β1, a potent profibrotic cytokine) and plasminogen activator inhibitor 1 (PAI-1) play important roles in the development of pulmonary fibrosis. The objective of the study was to investigate the association between the gene polymorphisms of TGF-β1 869 T > C and PAI-1 4G/5G and the susceptibility to IPF in Han ethnicity.

METHODSPolymerase chain reaction (PCR) and restriction fragment length polymorphism were performed to analyse the gene polymorphisms of TGF-β1 in 869T > C and PAI-1 4G/5G in 85 IPF patients and 85 healthy controls matched in age, gender, race and smoker status.

RESULTSThere was a significant difference in 869T > C genotype distribution of TGF-β1 between IPF cases and controls, a significant negative association between TC genotype and the development of IPF (OR = 0.508, 95%CI: 0.275 - 0.941) and a positive association between CC genotype and the development of IPF (OR = 1.967, 95%CI: 1.063 - 3.641). There was a significant positive association between PAI-1 5G/5G genotype and the development of IPF (OR = 0.418, 95%CI: 0.193 - 0.904).

CONCLUSIONSGene polymorphisms of TGF-β1 in 869T > C and PAI-1 4G/5G may affect the susceptibility to IPF in Han ethnicity. Further investigations are needed to confirm these findings and assess their biological significance in the development of the disease in this ethnic population.

Aged ; Case-Control Studies ; Female ; Genetic Predisposition to Disease ; genetics ; Humans ; Idiopathic Pulmonary Fibrosis ; genetics ; Male ; Middle Aged ; Plasminogen Activator Inhibitor 1 ; genetics ; Polymerase Chain Reaction ; Polymorphism, Genetic ; genetics ; Transforming Growth Factor beta1 ; genetics

The aim of the present study was to observe the effects of Notch1 and autophagy on extracellular matrix deposition in renal tubulointerstitium of diabetes and to explore the mechanism. The mice were randomly divided into normal control group (db/m mice) and diabetes group (db/db mice). After 12 weeks of feeding, the mice were sacrificed and the corresponding biochemical indexes were measured. Rat renal tubular epithelial cells NRK52E were cultured under normal glucose (NG) and high glucose (HG) respectively, and the expression of Notch1 and LC3 proteins were detected by Western blotting. Autophagosomes in NRK52E cells with overexpressed and knockdown Notch1 under NG and HG conditions were observed by confocal microscope, and the expression changes of Notch1, Collagen-I and III protein were detected by immunofluorescence. The results showed that the Notch1 and Collagen-III expressions were increased (P < 0.01) and the LC3 expression was decreased (P < 0.05) in db/db mice compared with db/m mice. In vitro, the Notch1 was increased (P < 0.01) and the LC3 expression was decreased significantly (P < 0.01) in NRK52E cells of HG group compared with NG group. There was no significant change of Notch1 and LC3 expression between the mannitol (MA) group and the NG group. Autophagy was decreased and extracellular matrix deposition was aggravated when Notch1 was overexpressed. In contrast, autophagy was increased and extracellular matrix deposition was relieved by knockdown of Notch1 under HG conditions. In conclusion, Notch1 protein expression was increased and autophagy was reduced in renal tissue of diabetes and renal tubular epithelial cells under HG. The extracellular matrix deposition in the renal tubulointerstitium was relieved by regulating autophagy after the knockdown of Notch1.
Animals ; Autophagy/physiology* ; Diabetes Mellitus ; Extracellular Matrix ; Glucose/pharmacology* ; Kidney ; Mice ; Rats ; Receptor, Notch1/genetics*