Indoxyl Sulfate Induces Renal Fibroblast Activation through a Targetable Heat Shock Protein 90-Dependent Pathway

<div>17-AAG blocks HSP90-dependent activation of the Smad pathway induced by IS in NRK-49F cells. (a) HSP90 intracellular localization after a 120-minute IS treatment with or without 17-AAG. Arrows indicate nuclear sites, where no immunopositivity occurred in the presence of 17-AAG. (b) Western blot of Smad 2/3 phosphorylation in cells treated for 120 minutes with IS, 17-AAG, and 17-AAG+IS, respectively. Results are normalized for total Smad 2/3. Values are expressed as fold <svg height="12.7112pt" id="M44" style="vertical-align:-3.403299pt" version="1.1" viewbox="-0.0498162 -9.3079 75.1994 12.7112" width="75.1994pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,0,0)"><path d="M390 111C344 68 312 56 269 56C212 56 118 102 118 241C118 346 175 401 241 401C277 401 312 388 342 360C350 352 355 349 361 349C372 349 394 371 394 392C394 403 391 411 378 422C362 436 329 449 288 449H287C250 449 190 432 138 392C71 341 37 274 37 197C37 90 112 -12 238 -12C297 -12 363 32 407 90L390 111Z"></path></g><g transform="matrix(.013,0,0,-0.013,5.421,0)"><path d="M513 0V26C455 31 447 37 447 103V278C447 398 390 449 309 449C255 449 202 412 166 376V712C127 700 67 684 19 677V653C85 647 87 643 87 580V103C87 37 79 31 19 26L18 0H231V26C171 32 166 39 166 103V341C194 373 232 392 270 392C337 392 368 351 368 269V103C368 38 360 32 302 26V0H513Z"></path></g><g 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330 22 240 22C152 22 124 173 124 313S148 602 238 602Z"></path></g><g transform="matrix(.013,0,0,-0.013,49.709,0)"><path d="M384 0V27C293 34 287 42 287 114V635C232 613 172 594 109 583V559L157 557C201 555 205 550 205 499V114C205 42 199 34 109 27V0H384Z"></path></g></svg>).</span> IS: indoxyl sulfate-treated cells; 17-AAG+IS: cells pretreated with the HSP90 inhibitor 17-AAG and then treated with IS.</div>

Oxidative Medicine and Cellular Longevity

fig6

Figure 6

Figure 6: Indoxyl Sulfate Induces Renal Fibroblast Activation through a Targetable Heat Shock Protein 90-Dependent Pathway 