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

• 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
• ISSN: 1567-2379; 1567-2387
• DOI: 10.1007/s10735-022-10078-6

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.