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Mechanical stretch induces angiotensinogen expression through PARP1 activation in kidney proximal tubular cells
- Source :
- In vitro cellulardevelopmental biology. Animal. 51(1)
- Publication Year :
- 2014
-
Abstract
- Poly(ADP-ribose) polymerase 1 (PARP1) contributes to fibrosis in several disease models. Recent in vivo data indicate that loss of PARP1 attenuates renal fibrosis and inflammation independent on transforming growth factor-β (TGF-β); however, the role of PARP1 in kidney tubular cells in response to tubulointerstitial fibrosis remains to be defined. Here, we report that PARP1 activation after mechanical stretch of kidney proximal tubular cells enhances angiotensinogen expression via nuclear factor kappa B (NF-κB) activation. Mechanical stretch for 24 h increased PARP1 expression and activation in mouse cortical proximal tubular (MCT) cells. Treatment with 3-aminobenzamide, a PARP1 inhibitor, efficaciously reduced the PARP1 activation induced by mechanical stretch. PARP1 inhibition also reduced angiotensinogen expression and NF-κB p65 phosphorylation induced by mechanical stretch. TGF-β1 expression and secretion were enhanced by mechanical stretch, but PARP1 inhibition did not change the levels of TGF-β1. These data demonstrate that mechanical stretch-induced PARP1 activation contributes to angiotensinogen expression and NF-κB activation in kidney proximal tubular cells, resulting in the promotion of renal tubulointerstitial fibrosis and inflammation.
- Subjects :
- medicine.medical_specialty
Angiotensinogen
Inflammation
Poly(ADP-ribose) Polymerase Inhibitors
Kidney Tubules, Proximal
Transforming Growth Factor beta1
Mice
Fibrosis
Internal medicine
medicine
Renal fibrosis
Animals
DNA (Cytosine-5-)-Methyltransferases
Enzyme Inhibitors
Phosphorylation
Cell Shape
Kidney
urogenital system
Chemistry
Transcription Factor RelA
Cell Biology
General Medicine
medicine.disease
Cell biology
Enzyme Activation
medicine.anatomical_structure
Endocrinology
Cell culture
Tubulointerstitial fibrosis
Stress, Mechanical
Stem cell
medicine.symptom
Poly(ADP-ribose) Polymerases
Developmental Biology
Transforming growth factor
Subjects
Details
- ISSN :
- 1543706X
- Volume :
- 51
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- In vitro cellulardevelopmental biology. Animal
- Accession number :
- edsair.doi.dedup.....ff591d3892dba56b07e380ba56418178