Arteriolar vascular smooth muscle cell differentiation in benign nephrosclerosis.
BACKGROUND
Benign nephrosclerosis (bN) is the most prevalent form of hypertensive damage in kidney biopsies. It is defined by early hyalinosis and later fibrosis of renal arterioles. Despite its high prevalence, very little is known about the contribution of arteriolar vascular smooth muscle cells (VSMCs) to bN. We examined classical and novel candidate markers of the normal contractile and the pro-fibrotic secretory phenotype of VSMCs in arterioles in bN.


METHODS
Sixty-three renal tissue specimens with bN and eight control specimens were examined by immunohistochemistry for the contractile markers caldesmon, alpha-smooth muscle actin (alpha-SMA), JunB, smoothelin and the secretory marker S100A4 and by double stains for caldesmon or smoothelin with S100A4.


RESULTS
Smoothelin immunostaining showed an inverse correlation with hyalinosis and fibrosis scores, while S100A4 correlated with fibrosis scores only. Neither caldesmon, alpha-SMA nor JunB correlated with hyalinosis or fibrosis scores. Cells in the arteriolar wall were exclusively positive either for caldesmon/smoothelin or S100A4.


CONCLUSIONS
This is the first systematic analysis of VSMC differentiation in bN. The results suggest that smoothelin is the most sensitive marker for the contractile phenotype and that S100A4 could be a novel marker for the secretory phenotype in vivo. The other markers did not seem to differentiate these phenotypes in bN. Thus, VSMC phenotype markers should be defined in the context of the vessel segment and disease under examination. S100A4 could not only be a marker of pro-fibrotic secretory VSMCs in bN but also an important mediator of arteriolar fibrosis.
Institute of Pathology, Hannover Medical School, Hannover, Germany.
Clemens Luitpold
CL
Bockmeyer
David Sebastian
DS
Kern
Vinzent
V
Forstmeier
Svjetlana
S
Lovric
Friedrich
F
Modde
Putri Andina
PA
Agustian
Sandra
S
Steffens
Ingvild
I
Birschmann
Jana
J
Traeder
Maximilian Ernst
ME
Dämmrich
Anke
A
Schwarz
Hans Heinrich
HH
Kreipe
Verena
V
Bröcker
Jan Ulrich
JU
Becker
D000328:Adult; D001160:Arterioles / Q000378:metabolism / Q000473:pathology*; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D002454:Cell Differentiation; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D009124:Muscle Proteins / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000473:pathology*; D009400:Nephrosclerosis / Q000378:metabolism / Q000473:pathology*; D011379:Prognosis; D055815:Young Adult
D015415:Biomarkers; D009124:Muscle Proteins