Key aspects of exosome biogenesis, cargo, and their link to autophagy in CP/CPPS.
| Aspect | Key components/Markers | Function/Significance | Link to autophagy in CP/CPPS |
|---|---|---|---|
| Biogenesis pathway | ESCRT complexes (ESCRT-0, -I, -II, -III), ALIX, TSG101 | Mediates inward budding of the endosomal membrane to form ILVs inside MVBs. | Autophagosomes can fuse with MVBs to form amphisomes, directly influencing exosome secretion and cargo [15, 41, 44]. |
| Key surface markers | Tetraspanins (CD63, CD81, CD9), HSP70, MHC classes | Used for exosome identification and isolation. Indicate endosomal origin, and can influence cellular uptake. | General principle: Cellular stress and altered autophagic flux can remodel the exosome surface proteome, potentially affecting biodistribution [10, 44, 45, 102]. CP/CPPS evidence: This specific link remains unexplored in prostate-derived exosomes. |
| Pro-inflammatory cargo | IL-1β, IL-18, TNF-α, HMGB1 (DAMP) | Drives inflammation and immune cell activation. Central to CP/CPPS pathology. | Impaired autophagy leads to the accumulation of these molecules inside the cell, increasing their loading into exosomes [6, 56, 103]. |
| Immunomodulatory miRNAs | miR-155, miR-21, miR-146a | Key regulators of immune responses (e.g., miR-155 promotes M1 macrophage polarization). | Autophagy regulates miRNA levels. Dysfunctional autophagy alters the miRNA profile of exosomes, shifting the immune response toward pro-inflammation [104–106]. |
| Pain and neural cargo | NGF, BDNF, cytokines | Mediates neuronal sensitization, contributing to chronic pelvic pain. | General principle: Exosomes from stressed cells (e.g., glial, cancer) carry pain mediators that directly sensitize sensory neurons, establishing a role in chronic pain [107, 108]. Specific link to autophagy: The hypothesis that autophagy deficiency in prostate cells enhances this exosomal pain signaling remains to be tested in CP/CPPS models. |
| Pro-fibrotic cargo | TGF-β1, fibronectin, collagen | Promotes differentiation of fibroblasts into myofibroblasts, leading to tissue fibrosis. | Autophagy is frequently induced by and required for TGF-β1 profibrotic signaling [109–111]. Inhibition of autophagy (e.g., ATG5/7 loss) attenuates TGF-β1-driven collagen/fibronectin production [109, 112]. The potential enhancement of exosomal TGF-β1 release under autophagy impairment remains less established. |
ATG: autophagy-related; BDNF: brain-derived neurotrophic factor; CP/CPPS: chronic prostatitis/chronic pelvic pain syndrome; DAMP: damage-associated molecular pattern; ESCRT: endosomal sorting complex required for transport; ILVs: intraluminal vesicles; MHC: major histocompatibility complex; MVBs: multivesicular bodies; NGF: nerve growth factor; TGF-β1: transforming growth factor beta 1; TNF-α: tumor necrosis factor-alpha.
DKN: Conceptualization, Investigation, Writing—original draft, Writing—review & editing, Visualization. FG: Formal analysis, Visualization. EDKF: Writing—review & editing. AA: Writing—review & editing, Data curation. BRO: Data curation, Visualization. FA: Data curation, Project administration. XZ: Supervision, Project administration, Writing—review & editing, Resources. All authors read and approved the submitted version.
The authors declare that they have no conflicts of interest.
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