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2015 ; 10
(9
): e0137028
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Variable Expression of Neural Cell Adhesion Molecule Isoforms in Renal Tissue:
Possible Role in Incipient Renal Fibrosis
#MMPMID26327314
Markovi?-Lipkovski J
; ?ivoti? M
; Müller CA
; Tampe B
; ?irovi? S
; Vje?tica J
; Tomanovi? N
; Zeisberg M
; Müller GA
PLoS One
2015[]; 10
(9
): e0137028
PMID26327314
show ga
Rare neural cell adhesion molecule (NCAM) positive cells have been previously
described within the normal human adult kidney interstitium, speculating that
they could increase in the interstitium with incipient interstitial renal
fibrosis (IRF). In the present study, among 93 biopsy samples of various kidney
diseases, NCAM+ interstitial cells were detected in 62.4% cases. An increased
number of NCAM+ cells was significantly observed only in incipient IRF compared
to normal renal tissues and advanced IRF stages (p<0.001), independently of
underlying diseases (p = 0.657). All three major NCAM isoforms' RT-PCR bands were
visible either in normal or in kidneys with incipient IRF, albeit their mRNA
expression levels measured by qRT-PCR were different. Applying qRT-PCR on pure
NCAM+ cells population, obtained by laser capture microdissection, significant
mRNA over-expression of NCAM140kD isoform was found in NCAM+ cells within
incipient IRF (p = 0.004), while NCAM120kD and NCAM180kD isoforms were not
changed significantly (p = 0.750; p = 0.704; respectively). Simultaneously,
qRT-PCR also showed significant ?SMA (p = 0.014) and SLUG (p = 0.004) mRNAs
up-regulation within the NCAM+ cells of incipient IRF, as well as highly
decreased matrix metalloproteinases (MMP) -2 and -9 mRNAs (p = 0.028; p = 0.036;
respectively). However, using double immunofluorescence MMP-9 could still be
detectable on the protein level in rare NCAM+ cells within the incipient IRF.
Further characterization of NCAM+ cells by double immunofluorescent labeling
revealed their association with molecules involved in fibrosis. Fibroblast growth
factor receptor 1 (FGFR1) and ?5?1 integrin were extensively expressed on NCAM+
cells within the incipient IRF areas, whereas human epididymis protein-4 (HE4)
was found to be present in few NCAM+ cells of both normal and interstitium with
incipient fibrosis. Heterogeneity of NCAM+ interstitial cells in normal and
incipient IRF, concerning molecules related to fibrosis and variable expression
of NCAM isoforms, could suggest diverse role of NCAM+ cells in homeostasis and in
regulation of renal fibrosis in diseased kidneys.
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