TGF-β1 receptor blockade attenuates unilateral ureteral obstruction-induced renal fibrosis in C57BL/6 mice through attenuating Smad and MAPK pathways

Renal fibrosis is characterized by accumulation of extracellular matrix components and collagen deposition. TGF-β1 acts as a master switch promoting renal fibrosis through Smad dependent and/or Smad independent pathways. Thirty-five male C57BL/6 mice were divided into five groups of seven each; sham...

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Bibliographic Details
Published in:Journal of molecular histology 2022-08, Vol.53 (4), p.691-698
Main Authors: Nazari Soltan Ahmad, Saeed, Kalantary-Charvadeh, Ashkan, Hamzavi, Masoud, Ezzatifar, Fatemeh, Aboutalebi Vand Beilankouhi, Elmira, Toofani-Milani, Attabak, Geravand, Faezeh, Golshadi, Zakieh, Mesgari-Abbasi, Mehran
Format: Article
Language:English
Subjects:
Biomedical and Life Sciences
Biomedicine
Cell Biology
Collagen
Developmental Biology
Extracellular matrix
Fibronectin
Fibrosis
Kidneys
Life Sciences
MAP kinase
Oral administration
Original Paper
Oxidation
Smad protein
Transforming growth factor-b1
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Summary:Renal fibrosis is characterized by accumulation of extracellular matrix components and collagen deposition. TGF-β1 acts as a master switch promoting renal fibrosis through Smad dependent and/or Smad independent pathways. Thirty-five male C57BL/6 mice were divided into five groups of seven each; sham, unilateral ureteral obstruction (UUO), UUO+galunisertib (150 and 300 mg/kg/day), galunisertib (300 mg/kg/day). The UUO markedly induced renal fibrosis and injury as indicated by renal functional loss, increased levels of collagen Iα1, fibronectin and α-SMA; it also activated both the Smad 2/3 and MAPKs pathways as indicated by increased levels of TGF-β1, p-Smad 2, p-Smad 3, p-p38, p-JNK and p-ERK. These UUO-induced changes were markedly attenuated by oral administration of galunisertib, the TGFβRI small molecule inhibitor. In conclusion, we demonstrated that TGF-β1 receptor blockade can prevent UUO-induced renal fibrosis through indirect modulation of Smad and MAPKs signaling pathways and may be useful as a therapeutic agent in treatment and/or prevention of renal fibrosis.
ISSN:1567-2379
1567-2387
DOI:10.1007/s10735-022-10078-6