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Microbes & Immunity PTMs in Sepsis: Mechanisms and therapy

enhancing lipopolysaccharide-induced macrophage profoundly impacts disease progression, suggesting that
inflammation. Conversely, ginkgolic acid inhibits targeting UBC9 and SENP1 may offer novel sepsis treatments.
91
SUMOyation, promoting NF-κB p65 phosphorylation and
nuclear translocation, increasing the release of macrophage 6. Acetylation and sepsis
inflammatory factors and apoptosis, thereby exacerbating Acetylation, a PTM catalyzed by acetyltransferase,
sepsis-induced organ damage. 92 modulates gene expression and participates in cellular
In summary, SUMOylation exerts an anti-inflammatory processes, including gene transcription and signal
5
and protective role in sepsis by stabilizing IκBα to inhibit transduction. Aberrant acetylation within the TLR4
NF-κB signaling, regulating macrophage polarization, signaling complex is implicated in dysregulated immune
inflammatory responses, and cell apoptosis. The dynamic responses, suggesting acetylation as a potential therapeutic
balance of the core regulatory nodes UBC9 and SENP1 target in sepsis. 93

Table 1. Roles of regulatory factors involved in different PTMs and the corresponding targets in sepsis
Targets Regulatory factors Impact on sepsis References
Phosphorylation
NF-κB MIR210HG, PGC-1α Promote 18,30
TIPE2, Ecn, KLF13, AST, PARK7, SHP-1, PVB Inhibit 26-29,31,41
MAPK Pin1, TLR4 Promote 45,47
THC, PVB, ADM2, artesunate, MaR1, fisetin, WIP1 Inhibit 37,38,40,41,43,44,48
STAT3 PLD2 Promote 53
Lyn, PEC, colchicine, 4-OI, MSCs Inhibit 52,54-57
PI3K/ATK HGF, S1P Promote 60,62
S1PR3, Ac2-26, Hibifolin, XBJ, BNP Inhibit 62,64-67
Ubiquitination
NLRP3 Cbl-b, RNF125, β-TrCP1, TIMP2 Promote 73,74,77
YAP, KBTBD7, HSPA8 Inhibit 74-76
Other target FBXW7 Promote 79
WWP2, CHIP, YL-109, samotolisib Inhibit 80-83
SUMOylation
NF-κB SENP1, GA Promote 91,92
UBC9, KLF4 Inhibit 88,90
Acetylation
SIRTs GITR Promote 99
GAS5, AVS, NMN, MK-4, Zn 2+ Inhibit 95-97,101,102
Lactylation
Histone METTL3, EGR1, RhoA Promote 105-107
Non-histone Fis1, HMGB1 Promote 21,109
PDHA1 Inhibit 21
Abbreviations: Ac2-26: Annexin A1; ADM2: Adrenomedullin 2; AST: Astragaloside IV; AVS: Nicaraven; BNP: Phenpropylline; Cb1-b: Casitas B-lineage
lymphoma proto-oncogene b; Ecn: Echinatin; EGR1: Early growth response protein 1; Fis1: Mitochondrial fission protein 1; GA: Ginkgolic acid;
GAS5: Growth arrest-specific transcript 5; GITR: Glucocorticoid-induced TNFR-related protein; HGF: Hepatocyte growth factor; HMGB1: High
mobility group box 1; HSPA8: Heat shock protein family A member 8; KLF: Kruppel-like factor; MaR1: Maresin-1; MIR210HG: MicroRNA-210
host gene; MK-4: Menadione 4; MSCs: Mesenchymal stem cells; NMN: Nicotinamide mononucleotide; 4-OI: 4-Octyl itaconate; PARK7: Parkinson’s
disease protein 7; PDHA1: Pyruvate dehydrogenase E1 component subunit α; PEC: Pectolinarigenin; PGC-1α: Peroxisome proliferator-activated
receptor gamma coactivator 1-alpha; Pin1: Peptidyl-prolyl cis/trans isomerase; PLD2: Phospholipase D2; PVB: Pinaverium bromide; S1P: Sphingosine
1-phosphate lyase; S1PR3: S1P receptor type 3; SENP1: SUMO-specific peptidase 1; SHP-1: Src homology region 2 domain-containing phosphatase-1;
THC: Tetrahydrocurcumin; TIMP2: Tissue inhibitor of metalloproteinase 2; TIPE2: TNF-α-induced protein 8-like 2; TLR4: Toll-like receptor 4;
β-TrCP1: Beta-transducin repeats-containing protein 1; UBC9: Ubiquitin-conjugating enzyme 9; WIP1: Wild-type p53-induced phosphatase 1; XBJ:
Xuebijing; YAP: Yes-associated protein.

Volume 2 Issue 3 (2025) 6 doi: 10.36922/MI025090016