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 fi...

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Main Authors: Chanyanuch Intachat, Phongsakorn Chuammitri, Benjaporn Sornpet, Prapas Patchanee, Nawin Manachai, Kakanang Piyarungsri
Format: Article
Language:English
Published: MDPI AG 2025-01-01
Series:Animals
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Online Access:https://www.mdpi.com/2076-2615/15/2/257
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Summary: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 <i>TGFβ</i>, <i>MAPK</i>, and <i>Bcl2</i> 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 <i>TGFβ</i> (<i>p</i> = 0.001) and considerable downregulation of <i>Bcl2</i> (<i>p</i> = 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 <i>TGFβ</i>, <i>MAPK</i>, or <i>Bcl2</i> 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.
ISSN:2076-2615