Nephroprotective effect of spexin in dogs and cats

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.