Nephroprotective effect of spexin in dogs and cats

TL;DR

This study explores how spexin (SPX) may protect kidney cells in dogs and cats with chronic kidney disease by reducing fibrosis and improving cell viability.

Contribution

The study is the first to show SPX's nephroprotective effects in canine and feline kidney cells and its anti-fibrotic role in chronic kidney disease.

Findings

SPX levels are significantly reduced in dogs and cats with chronic kidney disease.

SPX supplementation increases cell viability in MDCK and CRFK cells without affecting proliferation.

SPX reduces fibrotic markers like α-SMA, TIMP1, Col1a, and fibronectin in kidney cells.

Abstract

Kidney disease is a common and clinically significant problem in dogs and cats, yet the underlying pathophysiological mechanisms remain incompletely understood. A large part of the research concerns the role of newly described peptides/proteins that may potentially be involved in these processes. One of the peptides whose role in renal metabolism has not yet been fully understood is spexin (SPX), which has a wide distribution in the body and is involved in the regulation of many physiological processes. The aim of this study was to evaluate SPX concentration in serum from dogs and cats with chronic kidney disease (CKD) and to investigate the potential role of SPX in kidney cell metabolism using an in vitro model based on MDCK and CRFK cells.

Our findings showed a significant reduction in serum SPX levels in animals with CKD (p < 0.01). We also demonstrated, for the first time, the presence of SPX and its receptors GALR2 and GALR3 at the mRNA level in both cell lines. Moreover, we demonstrated that SPX supplementation increased cell viability in both cell lines (MDCK: p < 0.05; CRFK: p < 0.01), without affecting proliferation. Furthermore, SPX reduced the mRNA expression of key fibrotic markers associated with CKD progression, including α-SMA, TIMP1, Col1a, and fibronectin (p < 0.05). These effects were more pronounced following epithelial–mesenchymal transition (EMT) induction with TGF-β1 (p < 0.01).

Taken together, the obtained results indicate that SPX could be a regulator of kidney cell function and may be a potential therapeutic target in the treatment of kidney diseases in dogs and cats.

The online version contains supplementary material available at 10.1186/s12917-026-05316-y.

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