TGF-β1 expression and mesangial alterations in rat glomeruli of an experimental chronic nephrosis model

Yıl 2019, Cilt: 43 Sayı: 1, 6 - 12, 01.07.2019

İsmail Seçkin Mümin Uzunalan Meltem Ayaz Pekyak Sibel Köktürk Hüseyin Avni Sönmez Zeynep Banu Güngör Elif Yaprak Saraç Aslı Emincik Sibel Demirci Delipınar

Öz

Objective: Puromycine aminonucleoside
nephrosis (PAN) is extensively used as an experimental model of proteinuria
following podocyte injury. In PAN animal models, nephrotic syndrome with
minimal change disease and focal segmental sclerosis-like nephritis is
demonstrated to be similar to that in human; however, the real mechanism of PAN
is not yet elucidated. Evidence shows that transforming growth factor-β1
(TGF-β1) plays a key via stimulating matrix protein synthesis of both
glomerular epithelial and mesangial cells. In this study, we aimed to examine
the relationship between TGF-β expression and accumulation in mesangial matrix
(MM) by the changes in renal function and ultrastructure alterations in renal
glomeruli of the chronic PAN induced rats.

Methods: Twelve male Wistar albino rats
were divided into two groups: control group (n=6), chronic group (n=6). All
data was statistically analyzed by One-way ANOVA Test.

Results: Proteinuria levels in the chronic
nephrosis groups were greater than the control (p<0.0025) whereas the levels
of serum albumin and creatinine clearances were progressively decreased
(p<0.05). TGF-β1 expression and MM were both significantly increased in PAN
group. Ultrastructural images of glomeruli of PAN showed apoptotic endothelium
and mesangial cells, interstitial collagen and macrophages in increased MM.

Conclusion: Our findings suggest that
chronic PAN application induces a nephrotic syndrome, leading to renal
impairment by TGF-β1 expression in glomeruli, increase in MM, formation of
abundant interstitial collagen, and migration of macrophages. We suggest that
chronic PAN progressively increases TGF-β1 expression and apoptosis following
expansion of mesangial matrix in the affected glomeruli. This study needs
further researches to determine the main source and signal pathway of TGF-β1
expression by double staining methods.

Cite this article as: Seçkin İ, Uzunalan M,
Ayaz Pekpak M, Köktürk S, Sönmez HA, Güngör ZB. TGF-β1 expression and mesangial
alterations in rat glomeruli of an experimental chronic nephrosis model.
Cerrahpasa Med J 2019; 43(1): 6-12.

Anahtar Kelimeler

Mesangial matrix, puromycine aminonucleoside nephritis, TGF-β1, ultrastructure

Deneysel Kronik Nefroz Modeli Sıçan Glomerüllerinde TGF-b1 Ekspresyonu ve Mezangiyal Değişiklikler

Öz

Amaç: Puromisin aminonükleozid nefroz
(PAN), proteinüri ile seyreden podosit yaralanması modeli olarak yaygın bir
şekilde kullanılmaktadır. Deneysel olarak uyarılmış PAN hayvan modellerinde,
minimal değişikliklere sahip insan nefrotik sendromu ve fokal segmental
glomerulosklerozdakine benzer histolojik değişiklikler gösterilmiş, ancak etki
mekanizması tam olarak anlaşılamamıştır. Yapılan çalışmalar, çoğu kronik böbrek
hasarlarında, ekstrasellüler matriks (ESM) birikiminin görüldüğü ve bu süreçte
transforming büyüme faktörü-β1 (TGF-β1)’in anahtar bir rol oynadığı gösterilmiştir.  Bu çalışmada biz, kronik PAN uyarılı sıçan
böbrek glomerüllerinde, TGF-β1 ekspresyonu ve mezangial matriks (MM) birikimi
arasındaki ilişkiyi, böbrek fonksiyonu ve ultrastrüktürel değişikliklerle
incelemeyi amaçladık.

Yöntemler: Bu çalışma için 12 erkek Wistar
albino sıçan iki gruba ayrıldı: kontrol grubu ve kronik grup (n=6). Bütün
veriler istatistiksel olarak One-way ANOVA testi ile analiz edildi.

Bulgular: Proteinüri seviyeleri kronik
nefroz grubunda kontrolden yüksek (p<0,0025), serum albümin ve kreatinin
klirens değerleri ise oldukça düşüktü (p<0,05). PAN nefrozlu sıçanların
glomerüllerinde, hem TGF-β1 ekspresyonu hem de MM birikimi belirgin şekilde
artmıştı. Kronik PAN grubunun glomerüllerinin ultrastrüktürel görüntülerinde
artmış MM içerisinde apoptotik endotel ve mezangial hücrelere, interstisyal
kollajene ve makrofajlara rastladık.

Sonuç: Bulgularımız, kronik PAN
uygulamasının böbrek fonksiyonlarında bozulma ile birlikte, glomerülde TGF-β1
ekspresyonu, MM artışına, interstisyal kollajen oluşumuna ve makrofajların
göçüne neden olan bir nefrotik sendromu indüklediğini düşündürmektedir. Bu
çalışma, ikili işaretlemelerle TGF-β1’in ana kaynağının ve TGF-β1 sinyal
yolaklarının belirlenmesi için daha ileri çalışmalara ihtiyaç duymaktadır.

Cite this article as: Seçkin İ, Uzunalan M,
Ayaz Pekpak M, Köktürk S, Sönmez HA, Güngör ZB. TGF-β1 expression and mesangial
alterations in rat glomeruli of an experimental chronic nephrosis model.
Cerrahpasa Med J 2019; 43(1): 6-12.

Anahtar Kelimeler

Mezangial matriks, puromisin aminonükleozid nefroz, TGF-β1, ultrastrüktür

Kaynakça

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