Table 2.
Effects of HSPC/Hsp90 inhibition on intercellular junctions and tissue barriers.
| Hsp90 Inhibitor | Experimental System | Effects on Intercellular Junctions and Cytoskeleton | Reference |
|---|---|---|---|
| Radicicol | LPS-stimulated bovine pulmonary arterial endothelial cells (BPAEC) | Prevented LPS-induced TEER decrease; attenuated AJ disassembly; restored VE-cadherin levels | [65] |
| 17-AAG | LPS-stimulated human lung microvascular endothelial cells (HLMVEC) | Prevented LPS-induced TEER decrease; suppressed MLC phosphorylation | [66] |
| Radicicol, 17-AAG, or 17-DMAG | TGF-β-stimulated BPAEC | Prevented TGF-β-induced TEER decrease; attenuated AJ disassembly | [67] |
| AUY-922 | Hydrochloric acid-exposed HLMVEC | Attenuated acid-induced TEER decrease, AJ disassembly, and F-actin remodeling | [68] |
| AT 13387 or AUY-922 | SARS-CoV2 spike protein-stimulated HLMVEC | Attenuated spike protein-induced TEER decrease, AJ disassembly, and F-actin remodeling | [69] |
| 17-AAG | LPS-induced uvetitis in rats | Attenuated LPS-induced retinal vascular permeability; restored ZO-1 and occludin expression | [70] |
| 17-DMAG | Intracerebral hemorrhage in rats | Attenuated increased permeability of brain vasculature; partially restored ZO-1, occludin, and claudin-5 expression | [71] |
| 17-DMAG | Cerebral ischemic stroke in mice | Attenuated increased permeability of brain vasculature; partially restored ZO-1 and occludin expression | [72] |
| 17-DMAG | Traumatic brain injury in mice | Attenuated increased permeability of brain vasculature; partially restored ZO-1 and occludin levels | [73] |
| 17-AAG | Human corneal epithelial cells | Promoted AJ assembly | [74] |
| Geldanamycin | Colon cancer cells (HCT116) | Promoted AJ assembly | [75] |
| Ganetespib | HCT116 and HT-29 cells | Increased E-cadherin expression | [76] |
| Geldanamycin | Gα12-overexpressing MDCK cells | Attenuated Gα12-induced TEER decrease and TJ disassembly | [77] |
| shRNA-mediated knockdown of GRP94 | HeLa cells | Increased MLC phosphorylation and assembly of actomyosin stress fibers | [78] |
| Gp93 mutation that abrogates its tissue expression | Drosophila | Abnormal assembly of septate junctions in the intestinal epithelium | [79] |
| Inducible whole-body GRP94 knockout | Mice | Epithelial TJ disassembly in the ileum; bacterial translocation from the gut | [80] |
| Hepatocyte-specific GRP94 knockout | Mice | Disruption of AJs and gap junctions | [81] |