Unraveling TGF-β1's Role in Mediating Fibrosis and Cell Death in Feline Kidney Cells

Chronic kidney disease (CKD) is prevalent among older cats. The transforming growth factor beta 1 (TGF-β1) pathway is associated with renal fibrosis. TGF-β1 signaling through the non-canonical/smad-independent pathway activates mitogen-activated protein kinase (MAPK) signaling, which is linked to fibrosis and apoptosis. The MAPK pathway regulates the Bcl-2 protein family, which is known for its anti-apoptosis properties. This study aimed to quantify the mRNA expression of the TGFβ, MAPK, and Bcl2 genes and the protein expression of TGF-β1 and MAPK in feline kidney cells and tissue. A gene expression analysis was conducted using qPCR to calculate the relative gene expression, while the protein expression was assessed through Western blot analysis. Immunohistochemistry staining of TGF-β1 and MAPK was performed on feline kidney tissue. The results revealed the significant upregulation of TGFβ (p = 0.001) and considerable downregulation of Bcl2 (p = 0.010) in doxorubicin-treated feline kidney cells. The immunostaining levels of TGF-β1 and MAPK were higher in the kidney tissue of cats with CKD than in non-CKD cats. However, there was no difference in TGFβ, MAPK, or Bcl2 gene expression in CKD vs. non-CKD cats. The findings suggest that TGF-β1 and Bcl-2 are associated with renal fibrosis and apoptosis in feline kidney cells. A deeper understanding of the TGF-β1 pathway could enable veterinarians to monitor disease progression and mitigate complications in feline CKD.