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Sang, T.

Publications and source records attributed to Sang, T..

3 recordsLinked to original sources

Trem2hi macrophages bridge inflammation resolution and fibrosis initiation after ischemia-reperfusion injury in the kidney

Maladaptive repair of acute kidney injury (AKI) may lead to the development of chronic kidney disease (CKD) characterized by renal fibrosis. Macrophages play roles in AKI-to-CKD progression; however, the interplay between inflammation and fibrosis after AKI remains controversial and the precise role of the distinct macrophage subsets remains elusive. In the present study we identified a unique population of Trem2hi macrophages derived from the bone marrow as a mediator bridging inflammation resolution and fibrosis establishment after kidney injury. Trem2 deficient mice exhibited mitigated renal fibrosis after ischemia-reperfusion injury (IRI) while the renal injury and inflammation persisted. Mechanistically, Trem2 promoted renal inflammation resolution by facilitating macrophage efferocytosis to remove apoptotic tubule cells and reshaping the macrophage cytokine production profile. Loss of Trem2 expression led to excessive cholesterol accumulation in macrophages via Lxr-Abca1/Abcg1 axis and thus sustained pro-inflammatory cytokines production. Moreover, Trem2hi macrophages orchestrated the pro-fibrotic tubular epithelial cells and the activation of myofibroblasts through SPP1 to promote the establishment of renal fibrotic niche. Based on our findings, Trem2hi macrophages may serve as a potential therapeutic target for AKI-to-CKD in combination with anti-inflammatory remedies.

immunology↗

SnRK2-mediated phosphorylation of SIZ1 enhances global SUMOylation under osmotic stress in Arabidopsis

SUMOylation is a highly dynamic posttranslational modification that plays a critical role in regulating plant stress responses. The global SUMOylation is quickly induced by dehydration and hyperosmotic stresses in plants, while the detailed mechanism underlying such SUMOylation dynamics is largely unknown. Here, we report that the SNF1-related protein kinase 2 (SnRK2) and SUMO E3 ligase SIZ1 module is crucial for the stress-induced increment of SUMOylation in Arabidopsis. Under osmotic stress, or application of phytohormone Abscisic Acid (ABA), the rapidly activated SnRK2s physically interact with and phosphorylate SIZ1, enhancing its stability. The Ser820 residue in C-terminal region of SIZ1 proteins is a functional SnRK2 phosphosite, whose phosphorylation is abolished in the high-order mutant of SnRK2s. The non-phosphorylatable SIZ1S820A is unstable both in vivo and in vitro. We also noticed the degradation of SIZ1 is largely darkness-dependent, interestingly, independent of COP1, a key ubiquitin E3 ligase regulating photomorphogenesis. Multiple SUMOylation, Ubiquitination, and phosphorylation sites in SIZ1 proteins, which may coordinate the dynamics of SIZ1 proteins and global SUMOylation upon environmental changes. Our findings highlight the critical role of the SnRK2-SIZ1 module in regulating SUMOylation dynamics during plant stress responses and provide new insights into the regulatory mechanisms underlying this essential posttranslational modification.

plant biology↗

A cell-sorting-based nano-scale pipeline for cell-type-specific proteomics in plants

Multicellular organisms such as plants contain different cell types with specialized functions. Analyzing the characteristics of each cell type reveals specific cell functions and enhances understanding of organization and function at the organismal level. Here we report a highly-sensitive and efficient cell type-specific multiomics pipeline, combining simplified flow cytometry-based cell sorting for fluorescent protoplasts and optimized nanoscale proteomics and metabolomics methods, which allow in-depth analysis of the proteomes and metabolomes of a particular cell type. Using this method, we quantitatively compared the proteomes and metabolomes of guard cells and mesophyll cells and revealed that the enrichment of signal transduction-related proteins enables guard cells to respond rapidly to various environmental stimuli. We uncovered a guard cell-specific kinase cascade whereby RAF15 and OST1 mediate ABA-induced stomatal closure. This pipeline can be applied to various cell types in plant or non-plant systems to learn how cells function in highly organized multicellular organisms.

plant biology↗