Progress of small ubiquitin-related modifiers in kidney diseases

Abstract

Objective: Small ubiquitin-related modifiers (SUMOs) are a group of post-translational modification proteins extensively expressed in eukaryotes. Abnormal SUMOylation can lead to the development of various diseases. This article summarizes the progress on research of the role of SUMOs in various types of kidney diseases to further increase the understanding of the regulatory functions of SUMOylation in the pathogenesis of kidney diseases. Data sources: This review was based on articles published in the PubMed databases up to January 2018, using the keywords including “SUMOs,” “SUMOylation,” and “kidney diseases.” Study selection: Original articles and critical reviews about SUMOs and kidney disease were selected for this review. A total of 50 studies were in English. Results: SUMO participates in the activation of NF-κB inflammatory signaling pathway, playing a central regulatory role in the inflammation and progression of DN, and the secretion of various chemokines in AKI. SUMO involves in the regulation of TG2 and Nrf2 antioxidant stress, affecting renal tubular injury in AKI. SUMO affects the MAPK/ERK pathway, regulating intracellular signal transduction, modulating the transcription and expression of effector molecules in DN. SUMO contributes to the TGF-β/Smad pathway, leading to fibrosis of the kidney. The conjugate combination of SUMO and p53 regulates cell proliferation and apoptosis, and participates in the regulation of tumorigenesis. In addition, SUMOylation of MITF modulates renal tumors secondary to melanoma, Similarly, SUMOylation of tumor suppressor gene VHL regulates the occurrence of renal cell carcinoma in VHL syndrome. Conclusions: Tissue injury, inflammatory responses, fibrosis, apoptosis, and tumor proliferation in kidney diseases all involve SUMOs. Further research of the substrate SUMOylation and regulatory mechanisms of SUMO in kidney diseases will improve and develop new treatment measures and strategies targeting kidney diseases.

SUMOylation Landscape of Renal Cortical Collecting Duct Cells

“…DISCUSSION Kidney epithelial cells have to rapidly adapt to an ever-changing external environment and respond to a variety of cellular stresses, including osmotic, genotoxic and oxidative stresses 2 .As SUMOylation is a mechanism that alters the functional properties of a variety of proteins, or alters protein expression, it allows a diverse response of cells to various forms of stress. It is therefore not surprising that SUMOylated proteins are involved in human renal diseases, including acute kidney injury18 , renal cell carcinoma19 , and diabetic nephropathy20 . However, understanding the role of protein SUMOylation in the kidney was hampered by a lack of information regarding the magnitude of SUMOylation targets in the kidney.…”

“…Indeed, both the mineralocorticoid receptor (MR)42 and 11Beta-hydroxysteroid dehydrogenase type 243 , the enzyme that limits access of glucocorticoids to the MR, are SUMOylated. Furthermore, aldosterone plays a major role in renal inflammatory responses in diabetic kidney disease and a role of SUMOylation has been proposed20,44 . In line with an association between aldosterone and SUMOylation, in mpkCCD14 cells treated with aldosterone for 24 h SUMO labeling became more prominent in the perinuclear and nuclear regions, especially for SUMO2.…”

Poricoic acid A suppresses TGF‑β1‑induced renal fibrosis and proliferation via the PDGF‑C, Smad3 and MAPK pathways

“…The formation and progression of renal fibrosis is a complex and dynamic process that includes inflammatory cell infiltration, fibroblast activation and proliferation, ECM accumulation, tubular atrophy and microvascular degeneration (10,11). A number of genes have been reported to be involved in this process.…”

SENP1 modulates microglia‐mediated neuroinflammation toward intermittent hypoxia‐induced cognitive decline through the de‐SUMOylation of NEMO

“… 14 Evidence has demonstrated that SUMOylation participates in the NF‐κB pathway, playing an essential regulatory role in the inflammation and the secretion of various chemokines. 15 , 16 Almost all activators of NF‐κB depend on the release of IκB through activating an IκB kinase (IKK) complex that induces IκB degradation, allowing freed NF‐κB to translocate into the nucleus and activate the transcription of target genes. NEMO, an essential regulatory scaffolding subunit of IKK complex, indirectly regulates the activity of NF‐κB.…”