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

Chenguang Ding; Bo Wang; Xiang Feng Lai; Yingcong Guo; Greg Tesch; Xiaoming Ding; Jin Zheng; PuXun Tian; Sharon Ricardo; Hsin-Hui Shen; Wujun Xue

doi:10.1016/j.mtbio.2023.100716

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

Mater Today Bio. 2023 Jun 27:21:100716. doi: 10.1016/j.mtbio.2023.100716. eCollection 2023 Aug.

Authors

Chenguang Ding^{1

2}, Bo Wang³, Xiang Feng Lai³, Yingcong Guo^{1

2}, Greg Tesch⁴, Xiaoming Ding^{1

2}, Jin Zheng¹, PuXun Tian¹, Sharon Ricardo⁵, Hsin-Hui Shen³, Wujun Xue¹

Affiliations

¹ Department of Kidney Transplantation, Nephropathy Hospital, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, PR China.
² Institute of Organ Transplantation, Xi'an Jiaotong University, Xi'an, 710061, China.
³ Department of Materials Science and Engineering, Monash University, Clayton, Victoria, Australia.
⁴ Department of Nephrology and Monash University Department of Medicine, Monash Medical Centre, Clayton, Victoria, Australia.
⁵ Monash Biomedicine Discovery Institute, Department of Pharmacology, Monash University, Clayton, Victoria, Australia.

Abstract

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-β1 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.

Keywords: Cubosome; Kidney injury; mRNA.