Stretch reduces nephrin expression via an angiotensin II-AT 1-dependent mechanism in human podocytes: Effect of rosiglitazone

Ilaria Miceli, Davina Burt, Elena Tarabra, Giovanni Camussi, Paolo Cavallo Perin, Gabriella Gruden

Research output: Contribution to journalArticlepeer-review

52 Scopus citations


Increased glomerular permeability to proteins is a characteristic feature of diabetic nephropathy (DN). The slit diaphragm is the major restriction site to protein filtration, and the loss of nephrin, a key component of the slit diaphragm, has been demonstrated in both human and experimental DN. Both systemic and glomerular hypertension are believed to be important in the pathogenesis of DN. Human immortalized podocytes were subjected to repeated stretch-relaxation cycles by mechanical deformation with the use of a stress unit (10% elongation, 60 cycles/ min) in the presence or absence of candesartan (1 μM), PD-123319 (1 μM), and rosiglitazone (0.1 μM). Nephrin mRNA and protein expression were assessed using quantitative real-time PCR, immunoblotting, and immunofluorescence, and the protein expression of AT1 receptor and angiotensin II secretion were evaluated. Exposure to stretch induced a significant ∼50% decrease in both nephrin mRNA and protein expression. This effect was mediated by an angiotensin II-AT1 mechanism. Indeed, podocyte stretching induced both angiotensin II secretion and AT1 receptor overexpression, podocyte exposure to angiotensin II reduced nephrin protein expression, and both the AT-1 receptor antagonist candesartan and a specific anti-angiotensin II antibody completely abolished stretch-induced nephrin downregulation. Similar to candesartan, the peroxisome proliferator-activated receptor (PPAR)-γ agonist, rosiglitazone, also inhibited stretch-induced nephrin downregulation, suggesting interference with stretchinduced activation of the angiotensin II-AT1 receptor system. Accordingly, rosiglitazone did not alter stretch-induced angiotensin II secretion, but it prevented AT1 upregulation in response to stretch. These results suggest a role for hemodynamic stress in loss of nephrin expression and allude to a role of PPAR-γ agonists in the prevention of this loss.

Original languageEnglish (US)
Pages (from-to)F381-F390
JournalAmerican Journal of Physiology - Renal Physiology
Issue number2
StatePublished - Feb 2010
Externally publishedYes


  • AT receptor
  • Diabetic nephropathy
  • Proteinuria

ASJC Scopus subject areas

  • Physiology
  • Urology


Dive into the research topics of 'Stretch reduces nephrin expression via an angiotensin II-AT 1-dependent mechanism in human podocytes: Effect of rosiglitazone'. Together they form a unique fingerprint.

Cite this