Vol.7, No 1, 2000 pp. 31 -38
UC 612.12/.17
GLYCOSAMINOGLYCANS AND MYOFIBROBLASTS
MODULATE THE GLOMERULAR AND TUBULOINTERSTITIAL INJURY IN PRIMARY TYPE I
MESANGIOCAPILLARY GLOMERULONEPHRITIS
Ligia Petrica1, Marius Raica2, Adalbert Schiller1,
Silvia Velciov1, Gheorghe Gluhovschi1, Virginia Trandafirescu1,
Gheorghe Bozdog1, Cristina Gluhovschi1, Flaviu Bob1
University of Medicine and Pharmacy
1Department of Nephrology and 2Department of
Histology, County Hospital, Timişoara, Romania
Summary. Glycosaminoglycans (GAGs) play a crucial role in the layout
of the electro-ne--gative filter of the glomerular basement membrane (GBM)
and have a possible involvement in renal fibrosis. The expression of ?-smooth
muscle actin (?-SMA) amongst other cytoskeletal proteins, such as vimentin
(Vi), in the glomerulus and the intestitium correlates with glomerulosclerosis
(GSL) and tubulointerstitial fibrosis (TI). The purpose of the study
was to evaluate clinical, biochemical and histological aspects of primary
type I mesangiocapillary glomerulonephritis (MCGN) related to alterations
of GAGs deposits and to the expression of ?-SMA and Vi by glomerular and
interstitial cells.
A group of 28 patients (p) with primary type I MCGN was assessed
concerning blood pressure, proteinuria and serum creatinine. Kidney
biopsies were performed in all patients and were processed in light microsopy,
immunofluorescence and immunohisto-chemistry in order to reveal GAGs deposits,
Vi-and ?-SMA / PCNA (proliferating celll nuclear antigen) positive cells
in the glomerulus and the interstitium.
Of the 28 p, 19 p (67.85%) - group B presented with significant alterations
of GAGs in the capillaries, mesangium and interstitium, while 9 p (32.15%)
- group A, had a mild impairment of the distribution of GAGs only in the
capillary walls.
Linear regression analysis showed in both groups an inverse correlation
between GAGs staining in the capillaries and proteinuria and Ig deposits
in the capillary walls. In group B, we found an inverse correlation between
the GSL score and Vi expression in the glomerulus, and a direct correlation
between this score and glomerular ?-SMA and PCNA expression. TI injury
correlated positively with interstitial ?-SMA and PCNA. In group A, the
GSL score showed an inverse correlation with glomerular Vi, but did not
reveal a significant correlation with glomerular ?-SMA and PCNA. TI lesions
correlated weakly with intersititial ?-SMA alone. In group B, proteinuria
(P) and serum creatinine (SC) correlated inversely with glomerular Vi and
directly with glomerular and interstitial ?-SMA / PCNA. In group A, P showed
an inverse correlation with glomerular Vi, but no correlations with glomerular
and interstitial ?-SMA / PCNA; SC correlated inversely with glomerular
Vi and weakly with interstitial ?-SMA.
In conclusion, the alterations of GAGs deposits are significant in
primary type I MCGN and they correlate with the glomerular and interstitial
expression of ?-SMA and Vi. The biochemical picture of MCGN is far more
severe in these p and correlates with GSL and TI fibrosis.
Key words: Glomerulosclerosis, glycosaminoglycans, interstitial
fibrosis, mesangio-ca-pil-la-ry glomerulonephritis, myofibroblasts, proteinuria
GLIKOZAMINOGLIKANI I MIOFIBROBLASTI MODULIŠU
OŠTEĆENJE GLOMERULA I TUBULOINTERSTICIJUMA U PRIMARNOM MEZANGIOKAPILARNOM
GLOMERULONEFRITISU TIP I
Kratak sadržaj: Glikozaminoglikani (GAGs) igraju ključnu ulogu
u održavanju elektronegativnog naboja glomerulske bazalne membrane (GBM),
i moguća je njihova uloga u nastanku fibroze bubrega. Ekspresija ?-glatkomišićnog
aktina (?-SMA) u glomemlu i intersticijumu, uy druge citoskeletne proteine,
kao što je vimentin (Vi), koreliza sa glomerulosklerozom (GSL), tubulointersticijskom
fibrozom (TI). Cilj ovog rada je da se procene klinički, biohemijski i
histološki aspekti primarnog mezangiokapilarnog glomemlonefritisa
(MCGN) tip I u odnosu na promene GAGs deposita i ekspresiju ?-SMA i Vi
u glomenilskim i intersticijskim ćelijama.
Grupi od 28 bolesnika sa primarnim MCGN tip I određeni su krvni pritisak,
proteinurija i serumski kreatinin. U svih bolesnika učinjena bubrežna biopsija
pripremljena je za svetlosnu mikroskopiju, imunofluorescenciju i imunohistohemiju
u cilju otkrivanja GAGS depozita, Vi- i ?-SMA/PCNA (nuklearni antigen proliferišućih
ćelija) pozitivnih ćelija u glomerulu i intersticijumu.
Od 28 bolesnika, 19 bolesnika (67,85%) - grupa B, imalo je značajne
promene GAGs u kapilarima, mezangijumu i intersticijumu, dok je 9 bolesnika
(32,15%) - grupa A, imalo umerene promene distribucije GAGs, samo u zidovima
kapilara. Analiza linearne regresije pokazala je, u obema grupama, inverznu
korelaciju između GAGs bojenja u kapilarima i proteinurije te Ig depozita
u zidu kapilara. U grupi B nađena je inverzna korelacija između GSL skora
i ekspresije Vi u glomerulu, a direktna korelacija između ovog skora i
ekspresije u glomerulu ?-SMA i PCNA. Oštećenje TI koreliralo je pozitivno
sa ekspresijom u intersticijumu ?-SMA i PCNA. U grupi A, GLS skor je pokazao
inverznu korelaciju sa glomerulskim Vi, ali nije bilo značajne korelacije
sa glomerulskim ?-SMA i PCNA. Oštećenje TI koreliralo je jedino ali slabo
sa ekspresijom ?-SMA u intersticijumu. U grupi B, proteinurija (P) i serumski
kreatinin (SC) korelirali su inverzno sa vimentinom u glomerulima, a direktno
sa ?-SMA i PCNA u glomerulima i intersticijumu. U grupi A, P je inverzno
korelirala sa vimentinom u glomerulima, ali nije bilo korelacije sa ?-SMA
i PCNA u glomerulima i intersticijumu. SC je korelirao inverzno sa Vi u
glomerulima, a vrlo slabo sa ?-SMA u intersticijumu.
U zaključku, GAGs depoziti su značajni u primarnom PICGN tip I i korelišu
sa ekspresijom ?-SMA i Vi u glomerulu i intersticijumu. Biohemijski pokazatelji
su mnogo više oštećeni u ovih bolesnika, i korelišu sa GSL i TI fibrozom.
Ključne reči: Glomeruloskleroza, glikozaminoglikani, intersticijska
fibroza, mezangiokapilarni glomerulonefritis, miofibroblasti, proteinurija
