Minichromosome maintenance 6 protects against renal fibrogenesis by regulating DUSP6-mediated ERK/GSK-3β/Snail1 signaling

Jing Huang; Zhi-Feng Xu; Feng Liu; An-Ni Song; Hua Su; Chun Zhang

doi:10.1016/j.isci.2023.107940

Minichromosome maintenance 6 protects against renal fibrogenesis by regulating DUSP6-mediated ERK/GSK-3β/Snail1 signaling

iScience. 2023 Sep 16;26(10):107940. doi: 10.1016/j.isci.2023.107940. eCollection 2023 Oct 20.

Authors

Jing Huang¹, Zhi-Feng Xu¹, Feng Liu¹, An-Ni Song¹, Hua Su¹, Chun Zhang¹

Affiliation

¹ Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.

Abstract

Minichromosome maintenance 6 (MCM6) has been implicated in the progression of various malignant tumors; however, its exact physiological function in kidney diseases remains unclear. Here, we demonstrated that MCM6 levels showed a significant increase in the proximal tubular cells during progressive renal fibrosis in two unrelated in vivo fibrotic models, including unilateral ureteral obstruction (UUO) and unilateral ischemia-reperfusion injury (UIRI). Depletion of MCM6 aggravated partial epithelial-mesenchymal transition, extracellular matrix accumulation, and myofibroblast activation in the kidneys of UUO or UIRI mice. Conversely, overexpression of MCM6 promoted the recovery of E-cadherin and retarded UUO- or UIRI-induced renal fibrosis. In addition, DUSP6 expression substantially decreased in fibrotic kidneys, and it might be involved in MCM6-induced renal fibrosis by regulating the activation of ERK/GSK-3β/Snail1 signaling. In conclusion, our results highlight the significance of MCM6 in renal fibrosis, providing a potential therapeutic target for patients with chronic kidney disease.

Keywords: Fibrosis; Gene network; Model organism; Molecular interaction.