Oxalate induces the ossification of RTECs by activating the JAK2/STAT3 signaling pathway and participates in the formation of kidney stones

Background: The ossification of renal tubular epithelial cells (RTECs) plays an important initial role in the formation of kidney stones, but its specific mechanism is still unclear. The JAK2/STAT3 signaling pathway is important for bone cell differentiation. Accordingly, we explored the role and mechanism of the JAK2/STAT3 signaling pathway in the ossification of RTECs.

Methods: We used oxalate or ethylene glycol to construct kidney stone models in vitro and in vivo, and investigated the expression of osteogenic-specific genes, osteogenesis ability, and JAK2/STAT3 signaling in the kidney stone models by western blotting, qRT-PCR, immunofluorescence, and immunohistochemistry. Then, genetic engineering or drugs were used to inhibit the expression or activation of JAK2, and the expression of osteogenic-specific genes and the osteogenic ability of the RTECs were determined again.

Results: In the in vitro and in vivo kidney stone models, the expression of osteogenic specific genes in the RTECs was significantly upregulated, the osteogenic capacity was significantly increased, and the expression of p-JAK2 (phospho-JAK2) and p-STAT3 (phospho-STAT3) was significantly increased. When the expression or activation of JAK2 was inhibited, the ossification of RTECs and the formation of kidney stones was reversed.

Conclusions: During the formation of kidney stones, RTECs undergo obvious ossification, and the JAK2/STAT3 signaling pathway plays a key positive regulatory role in this process.