Scientists Discover Novel Function of RUNX1 in Renal Tubular Epithelial-to-Mesenchymal Transition and Fibrosis

Dr. Hongyan Wang from Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences and Dr. Tong Zhou from Ruijin Hospital, Shanghai Jiao Tong University publish their collaborated work in EBioMedicine, which is titled “Runt-related transcription factor 1 (RUNX1) promotes TGF-β-induced renal tubular epithelial-to-mesenchymal transition (EMT) and renal fibrosis through the PI3K subunit p110δ”.

Renal fibrosis is characterized by excessive deposition of extracellular matrix in kidney, and leads to renal failure in various chronic kidney diseases. Epithelial-to-mesenchymal transition (EMT) plays critical roles in the pathogenesis of renal fibrosis. It is important to identify the new effectors that could regulate EMT during the development of renal fibrosis.

Transcription factor RUNX1 is a master transcription factor in hematopoietic cells. Maocai Luo from Dr. Wang and Dr. Zhou’s lab s has previously identified the role of RUNX1 in macrophages to promote TLR4-induced inflammation. Importantly, they have identified that the RUNX1 inhibitor could block LPS-induced sepsis (JBC, 2016). Recently the role of RUNX1 in non-immune cells has received much attention. In this work, they have identified that RUNX1 expression is upregulated in renal fibrosis via the TGF-β-SMAD3 dependent manner. Importantly, specific deletion of RUNX1 in mouse renal tubular epithelial cells (RTECs) attenuates renal EMT and kidney fibrosis in response to unilateral ureteral obstruction (UUO) or folic acid (FA) treatment. Deficiency of RUNX1 also attenuates renal inflammation with the improved renal function. The underlying mechanism is that RUNX1 increases expression levels of the PI3K subunit p110δ and activates Akt, which promotes renal EMT and fibrosis.

This work was financially supported by grants from the National Natural Science Foundation of China, the Ministry of Science and Technology of China and the Chinese Academy of Sciences. Thanks for technique supports from the Core Facility of Cell Biology and Molecular Biology, and Animal Core Facility in Shanghai Institute of Biochemistry and Cell Biology (SIBCB), Chinese Academy of Sciences.

See the full article: