Cellular delivery of relaxin-2 mRNA as a potential treatment for kidney fibrosis

Renal fibrosis is a pathological feature of chronic kidney disease and its progression correlates with kidney function impairment. Since there are currently no specific therapies for renal fibrosis, we explored whether inducing local production of the anti-fibrotic molecule relaxin-2 in kidney cells has potential as a strategy for suppressing the development of renal fibrosis. Our study examined whether delivery of relaxin-2 mRNA to kidney cells in vitro and in vivo could inhibit mechanisms leading to renal fibrosis. Transfecting relaxin-2 mRNA into cultured kidney cells inhibited fibrotic responses to TGF-& beta;1 in an autocrine or paracrine manner by reducing fibrotic gene expression in kidney tubules, and reducing proliferation in kidney fibroblasts and mesangial cells. Similarly, cubosomes assisted delivery of relaxin-2 mRNA to mouse kidneys alleviated the fibrosis and inflammation associated with renal injury following unilateral ureter obstruction (UUO). Therefore, relaxin-2 mRNA exhibits potential as a novel therapy for inhibiting fibrosis and inflammation in chronic kidney disease.

Automated summary

Renal fibrosis, a common manifestation of chronic kidney disease, can be suppressed by inducing local production of relaxin-2 mRNA in kidney cells. In both in vitro and in vivo experiments, delivery of relaxin-2 mRNA reduced fibrotic gene expression and cell proliferation, inhibiting the development of renal fibrosis. The use of cubosomes as delivery vehicles for relaxin-2 mRNA also alleviated fibrosis and inflammation in a mouse model of renal injury. Therefore, relaxin-2 mRNA shows potential as a novel therapy for inhibiting fibrosis and inflammation in chronic kidney disease.