Deciphering the SUMO code in the kidney

Abstract

SUMOylation of proteins is an important regulatory element in modulating protein function and has been implicated in the pathogenesis of numerous human diseases such as cancers, neurodegenerative diseases, brain injuries, diabetes, and familial dilated cardiomyopathy. Growing evidence has pointed to a significant role of SUMO in kidney diseases such as DN, RCC, nephritis, AKI, hypertonic stress and nephrolithiasis. Recently, emerging studies in podocytes demonstrated that SUMO might have a protective role against podocyte apoptosis. However, the SUMO code responsible for beneficial outcome in the kidney remains to be decrypted. Our recent experiments have revealed that the expression of both SUMO and SUMOylated proteins is appreciably elevated in hypoxia‐induced tubular epithelial cells (TECs) as well as in the unilateral ureteric obstruction (UUO) mouse model, suggesting a role of SUMO in TECs injury and renal fibrosis. In this review, we attempt to decipher the SUMO code in the development of kidney diseases by summarizing the defined function of SUMO and looking forward to the potential role of SUMO in kidney diseases, especially in the pathology of renal fibrosis and CKD, with the goal of developing strategies that maximize correct interpretation in clinical therapy and prognosis.

Resveratrol Attenuates Inflammatory Bowel Disease in Mice by Regulating SUMO1

“…26) One of the obvious functions of SUMO1 is its ability to bind to β-catenin and enhance transcriptional activity. 13) Moreover, the activation of β-catenin is closely related to the malignant transformation of colon and upper gastrointestinal adenocarcinoma. 27,28) Although Wnt signaling is not the mainstream inflammatory pathway, there is increasing evidence that it can be used as a driver of injury repair.…”

“…[9][10][11] In addition, SUMO1 is also involved in the regulation of signaling pathways such as nuclear factor-kappaB (NF-κB), Wnt/β-catenin, transforming growth factor-β (TGF-β) and c-Jun N-terminal kinase (JNK). 12,13) Based on the characteristics of SUMO1, it plays an important role in many diseases such as inflammation-related diseases, tumors, and kidney diseases. [14][15][16] In our study, we researched the role of resveratrol in inhibiting the expression of SUMO1 and the Wnt/β-catenin pathway in dextran sodium sulfate (DSS)-induced IBD.…”

SUMO1 modification of IGF-1R combining with SNAI2 inhibited osteogenic differentiation of PDLSCs stimulated by high glucose

“…Sumoylation of proteins is an important regulatory element regulating protein function in the human body, which is involved in the pathogenesis of a variety of human diseases. More and more evidence have shown that sumoylation played important roles in the pathogenesis of diabetes [ 41 ]. However, we unexpectedly found that sumoylation of IGF-1R played a significant role in the process of stem cell osteogenic differentiation, especially in regulating downstream osteogenic-related transcription factors such as SNAI2 and RUNX2.…”

Krϋppel‐like factor 15 suppresses renal glomerular mesangial cell proliferation via enhancing P53 SUMO1 conjugation

“…Emerging evidence has indicated that SUMOylation and deSUMOylation play roles in numerous nephropathic diseases, such as renal dysgenesis, renal carcinoma, glomerular disease, podocyte apoptosis, renal medulla hypertonicity, acute kidney injury and nephrolithiasis 47‐51 . To clarify the relationship among KLF15, SUMO1, P53 SUMOylation and MC proliferation, we performed a series of transfection treatments on cells that had undergone PDGF‐BB‐induced proliferation.…”