NADPH Oxidase-Induced NALP3 Inflammasome Activation Is Driven by Thioredoxin-Interacting Protein Which Contributes to Podocyte Injury in Hyperglycemia

<div>Inhibiting either TXNIP or NADPH oxidase partially preserves the arrangement of F-actin fibers in podocytes exposed to HG. (a) Microscopic images of F-actin by rhodamine-phalloidin staining. (b) Summarized data from counting the cells with distinct, longitudinal F-actin fibers. Scoring was determined from 100 podocytes on each slide (<svg height="8.66698pt" id="M70" style="vertical-align:-0.2129993pt" version="1.1" viewbox="-0.0498162 -8.45398 29.0065 8.66698" width="29.0065pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.0135,0,0,-0.0135,0,0)"><path d="M495 86L479 114C446 82 419 66 409 66C401 66 401 72 406 97C420 166 436 231 453 297C489 435 454 448 428 448C406 448 384 439 354 422C305 394 222 327 161 247H159L183 345C200 415 194 448 173 448C143 448 82 410 23 351L38 325C64 349 95 371 105 371C111 371 116 365 109 336L25 -4L31 -12C50 -4 77 3 107 9C119 69 132 122 145 168C197 254 321 381 370 381C387 381 393 374 378 305L329 95C309 17 320 -12 345 -12C372 -12 430 19 495 86Z" id="g113-111"></path><glyph.data ascent="3473" descent="-2876" horiz-adv-x="502" vert-adv-y="502"></glyph.data></g><g transform="matrix(.0135,0,0,-0.0135,10.586,0)"><path d="M535 323V373H52V323H535ZM535 138V188H52V138H535Z" id="g117-34"></path><glyph.data ascent="3473" descent="-2876" horiz-adv-x="587" vert-adv-y="587"></glyph.data></g><g transform="matrix(.0135,0,0,-0.0135,22.324,0)"><path d="M153 550H386L412 615L406 623H120L82 318C104 327 142 338 184 338C294 338 347 275 347 187C347 112 305 39 221 39C160 39 119 71 97 89C88 97 80 96 71 90C59 80 50 67 49 57C48 45 52 36 66 23C80 9 123 -12 169 -12C221 -11 288 15 342 59C403 109 431 165 431 225C431 308 366 395 238 395C212 395 165 379 127 364L153 550Z" id="g113-54"></path><glyph.data ascent="3473" descent="-2876" horiz-adv-x="480" vert-adv-y="480"></glyph.data></g></svg>). Ctrl: control; HG: high glucose; Veh: vehicle; Scram: scrambled shRNA; shTXNIP: TXNIP shRNA; shgp91: <svg height="16.3177pt" id="M71" style="vertical-align:-3.5447pt" version="1.1" viewbox="-0.0498162 -12.773 47.6664 16.3177" width="47.6664pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.0135,0,0,-0.0135,0,0)"><path d="M463 437C426 431 375 425 327 422C297 440 264 449 231 449H230C153 449 51 396 51 283C51 215 94 168 139 149C123 129 91 103 51 88C50 78 53 60 62 46C75 25 100 2 136 -9C112 -28 73 -59 53 -79C38 -94 29 -113 29 -135C30 -192 91 -257 203 -257C336 -257 452 -160 452 -59C452 39 371 59 309 59C275 59 240 58 203 58C158 58 140 77 140 96C140 110 157 129 170 138C186 135 205 133 221 133C306 133 396 185 396 293C396 328 384 360 366 381L423 378C439 387 459 413 468 429L463 437ZM219 418C277 418 314 362 314 284C314 205 275 166 231 165C176 165 137 221 137 299C137 376 177 418 219 418ZM241 -11C285 -11 314 -14 339 -24C367 -36 384 -61 384 -95C384 -157 335 -206 240 -206C166 -206 108 -165 108 -110C108 -82 128 -54 154 -32C172 -17 195 -11 241 -11Z" id="g190-104"></path><glyph.data ascent="989" descent="-360" horiz-adv-x="468" vert-adv-y="468"></glyph.data></g><g transform="matrix(.0135,0,0,-0.0135,6.341,0)"><path d="M169 380V459C122 440 66 423 24 416V392C86 384 90 382 90 317V-135C90 -201 81 -207 17 -213V-240H253V-213C176 -207 169 -201 169 -125V6C182 -1 208 -11 238 -12C368 12 487 109 487 260C487 358 421 449 310 449C298 449 279 444 261 433L169 380ZM169 346C196 367 237 389 269 389C341 389 403 329 403 221C403 109 347 37 263 37C228 37 191 53 169 76V346Z" id="g190-113"></path><glyph.data ascent="989" descent="-360" horiz-adv-x="524" vert-adv-y="524"></glyph.data></g><g transform="matrix(.0135,0,0,-0.0135,13.49,0)"><path d="M244 635C114 635 38 519 38 422C38 317 111 240 217 240C236 240 255 244 277 256L345 292C311 140 203 39 59 15L64 -15C89 -15 150 -5 204 17C339 72 440 202 440 386C440 521 368 635 244 635ZM228 602C326 602 352 479 352 390C352 370 351 347 348 324C327 308 293 296 258 296C174 296 124 369 124 458C124 517 152 602 228 602Z" id="g113-58"></path><glyph.data ascent="3473" descent="-2876" horiz-adv-x="480" vert-adv-y="480"></glyph.data></g><g transform="matrix(.0135,0,0,-0.0135,19.995,0)"><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" id="g113-50"></path><glyph.data ascent="3473" descent="-2876" horiz-adv-x="480" vert-adv-y="480"></glyph.data></g><g transform="matrix(.0095,0,0,-0.0095,26.545,-5.984)"><path d="M573 302C573 402 527 451 414 451C386 451 343 446 313 437L330 513L320 522C295 508 261 484 243 463L230 415C194 400 159 383 126 359L131 330C159 344 187 357 222 368L109 -147C96 -204 80 -214 18 -223L13 -255L256 -244L259 -212L236 -210C184 -205 180 -195 191 -141L219 -1C240 -10 268 -12 284 -12C352 4 431 48 484 104C543 166 573 240 573 302ZM481 290C481 165 381 37 305 37C280 37 249 56 235 71L302 395C328 399 353 402 372 402C427 402 481 378 481 290Z" id="g50-113"></path><glyph.data ascent="3443" descent="-2856" horiz-adv-x="597" vert-adv-y="597"></glyph.data></g><g transform="matrix(.0095,0,0,-0.0095,32.208,-5.984)"><path d="M509 90L493 118C465 91 427 70 418 70S409 77 415 103L469 327C494 429 466 451 436 451C412 451 387 444 356 427C307 400 222 342 160 264H158L246 667C253 701 252 710 243 710C228 710 169 680 87 673L83 644H117C155 644 160 640 149 588L24 -4L32 -12C57 -4 86 4 108 9L143 187C198 275 324 386 375 386C394 386 399 367 385 311L331 87C315 22 322 -12 351 -12C387 -12 452 24 509 90Z" id="g50-105"></path><glyph.data ascent="3443" descent="-2856" horiz-adv-x="527" vert-adv-y="527"></glyph.data></g><g transform="matrix(.0095,0,0,-0.0095,37.206,-5.984)"><path d="M452 282C452 397 389 451 302 451C268 451 227 441 188 422C95 377 24 281 24 154C24 65 70 -12 173 -12C240 -12 297 16 342 52C418 113 452 201 452 282ZM359 282C359 163 308 66 247 39C237 35 225 32 212 32C151 32 114 79 114 157C114 301 180 380 223 398C240 405 250 408 265 408C315 408 359 369 359 282Z" id="g50-112"></path><glyph.data ascent="3443" descent="-2856" horiz-adv-x="476" vert-adv-y="476"></glyph.data></g><g transform="matrix(.0095,0,0,-0.0095,41.597,-5.984)"><path d="M545 403C545 425 527 451 498 451C448 451 400 404 312 286L290 341C262 412 246 451 219 451C182 451 138 404 92 345L112 323C152 368 169 378 181 378C192 378 201 359 216 321L257 214C184 115 142 69 113 69C102 69 93 73 88 79S78 89 68 89C47 89 24 61 24 40C24 8 49 -12 75 -12C125 -12 175 31 271 175L312 64C330 15 357 -12 382 -12C421 -12 475 35 515 98L496 121C466 88 439 62 420 62C402 62 384 92 363 147L325 247C349 280 374 309 397 333C422 361 446 381 462 381C471 381 481 374 488 366C493 360 499 357 505 357C521 357 545 380 545 403Z" id="g50-121"></path><glyph.data ascent="3443" descent="-2856" horiz-adv-x="569" vert-adv-y="569"></glyph.data></g></svg> shRNA; APO: apocynin; DPI: diphenyleneiodonium. <svg height="14.52pt" id="M72" style="vertical-align:-3.993601pt" version="1.1" viewbox="-0.0498162 -10.5264 53.0403 14.52" width="53.0403pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.0095,0,0,-0.0095,0,-5.984)"><path d="M486 158C486 177 478 202 466 220C413 228 386 236 336 262C386 288 413 297 466 304C478 323 486 347 485 366C470 376 444 381 422 380C389 338 368 319 321 288C323 345 329 372 349 422C339 442 322 461 305 470C289 461 271 442 262 422C281 372 287 345 290 288C243 319 222 338 189 380C167 381 142 376 125 366C125 347 133 322 145 304C198 296 225 288 275 262C225 236 198 227 145 220C133 201 125 177 126 158C141 148 167 143 189 144C222 186 243 205 290 236C288 179 282 152 262 102C272 82 289 63 306 54C322 63 340 82 350 102C330 152 324 179 321 236C368 205 390 186 422 144C444 143 470 148 486 158Z" id="g50-43"></path><glyph.data ascent="3443" descent="-2856" horiz-adv-x="611" vert-adv-y="611"></glyph.data></g><g transform="matrix(.0135,0,0,-0.0135,6.314,1.006)"><path d="M600 480C600 590 528 650 384 650H143L137 622C222 614 225 607 210 531L130 127C113 41 106 36 23 28L17 0H294L300 28C204 36 195 42 212 127L243 284L314 263C327 263 339 263 352 264C465 271 600 337 600 480ZM508 481C508 351 402 304 329 304C289 304 265 311 250 317L295 559C302 594 310 606 323 611C335 616 350 619 367 619C455 619 508 573 508 481Z" id="g113-81"></path><glyph.data ascent="3473" descent="-2876" horiz-adv-x="617" vert-adv-y="617"></glyph.data></g><g transform="matrix(.0135,0,0,-0.0135,18.49,0)"><path d="M512 -3V55L134 254V256L512 456V514L75 281V230L512 -3Z" id="g117-91"></path><glyph.data ascent="3473" descent="-2876" horiz-adv-x="587" vert-adv-y="587"></glyph.data></g><g transform="matrix(.0135,0,0,-0.0135,30.228,0)"><path d="M241 635C89 635 35 457 35 312C35 153 89 -12 240 -12C390 -12 443 166 443 312C443 466 390 635 241 635ZM238 602C329 602 354 454 354 312C354 172 330 22 240 22C152 22 124 173 124 313S148 602 238 602Z" id="g113-49"></path><glyph.data ascent="3473" descent="-2876" horiz-adv-x="480" vert-adv-y="480"></glyph.data></g><g transform="matrix(.0135,0,0,-0.0135,36.731,0)"><path d="M113 -12C146 -12 170 11 170 46C170 78 146 103 114 103S58 78 58 46C58 11 82 -12 113 -12Z" id="g113-47"></path><glyph.data ascent="3473" descent="-2876" horiz-adv-x="228" vert-adv-y="228"></glyph.data></g><g transform="matrix(.0135,0,0,-0.0135,39.82,0)"><path d="M241 635C89 635 35 457 35 312C35 153 89 -12 240 -12C390 -12 443 166 443 312C443 466 390 635 241 635ZM238 602C329 602 354 454 354 312C354 172 330 22 240 22C152 22 124 173 124 313S148 602 238 602Z" id="g113-49"></path><glyph.data ascent="3473" descent="-2876" horiz-adv-x="480" vert-adv-y="480"></glyph.data></g><g transform="matrix(.0135,0,0,-0.0135,46.323,0)"><path d="M153 550H386L412 615L406 623H120L82 318C104 327 142 338 184 338C294 338 347 275 347 187C347 112 305 39 221 39C160 39 119 71 97 89C88 97 80 96 71 90C59 80 50 67 49 57C48 45 52 36 66 23C80 9 123 -12 169 -12C221 -11 288 15 342 59C403 109 431 165 431 225C431 308 366 395 238 395C212 395 165 379 127 364L153 550Z" id="g113-54"></path><glyph.data ascent="3473" descent="-2876" horiz-adv-x="480" vert-adv-y="480"></glyph.data></g></svg> compared with Ctrl; <svg height="16.005pt" id="M73" style="vertical-align:-3.993599pt" version="1.1" viewbox="-0.0498162 -12.0114 51.8599 16.005" width="51.8599pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.0095,0,0,-0.0095,0,-5.984)"><path d="M457 455H370L403 612H360L326 455H218L252 612H210L175 455H77L68 394H161L132 257H31L20 196H117L77 19H120L159 196H268L230 19H272L311 196H402L412 257H325L355 394H447L457 455ZM313 394L283 257H175L204 394H313Z" id="g58-33"></path><glyph.data ascent="1007" descent="-369" horiz-adv-x="487" vert-adv-y="487"></glyph.data></g><g transform="matrix(.0135,0,0,-0.0135,5.134,1.006)"><path d="M600 480C600 590 528 650 384 650H143L137 622C222 614 225 607 210 531L130 127C113 41 106 36 23 28L17 0H294L300 28C204 36 195 42 212 127L243 284L314 263C327 263 339 263 352 264C465 271 600 337 600 480ZM508 481C508 351 402 304 329 304C289 304 265 311 250 317L295 559C302 594 310 606 323 611C335 616 350 619 367 619C455 619 508 573 508 481Z" id="g113-81"></path><glyph.data ascent="3473" descent="-2876" horiz-adv-x="617" vert-adv-y="617"></glyph.data></g><g transform="matrix(.0135,0,0,-0.0135,17.31,0)"><path d="M512 -3V55L134 254V256L512 456V514L75 281V230L512 -3Z" id="g117-91"></path><glyph.data ascent="3473" descent="-2876" horiz-adv-x="587" vert-adv-y="587"></glyph.data></g><g transform="matrix(.0135,0,0,-0.0135,29.047,0)"><path d="M241 635C89 635 35 457 35 312C35 153 89 -12 240 -12C390 -12 443 166 443 312C443 466 390 635 241 635ZM238 602C329 602 354 454 354 312C354 172 330 22 240 22C152 22 124 173 124 313S148 602 238 602Z" id="g113-49"></path><glyph.data ascent="3473" descent="-2876" horiz-adv-x="480" vert-adv-y="480"></glyph.data></g><g transform="matrix(.0135,0,0,-0.0135,35.55,0)"><path d="M113 -12C146 -12 170 11 170 46C170 78 146 103 114 103S58 78 58 46C58 11 82 -12 113 -12Z" id="g113-47"></path><glyph.data ascent="3473" descent="-2876" horiz-adv-x="228" vert-adv-y="228"></glyph.data></g><g transform="matrix(.0135,0,0,-0.0135,38.64,0)"><path d="M241 635C89 635 35 457 35 312C35 153 89 -12 240 -12C390 -12 443 166 443 312C443 466 390 635 241 635ZM238 602C329 602 354 454 354 312C354 172 330 22 240 22C152 22 124 173 124 313S148 602 238 602Z" id="g113-49"></path><glyph.data ascent="3473" descent="-2876" horiz-adv-x="480" vert-adv-y="480"></glyph.data></g><g transform="matrix(.0135,0,0,-0.0135,45.143,0)"><path d="M153 550H386L412 615L406 623H120L82 318C104 327 142 338 184 338C294 338 347 275 347 187C347 112 305 39 221 39C160 39 119 71 97 89C88 97 80 96 71 90C59 80 50 67 49 57C48 45 52 36 66 23C80 9 123 -12 169 -12C221 -11 288 15 342 59C403 109 431 165 431 225C431 308 366 395 238 395C212 395 165 379 127 364L153 550Z" id="g113-54"></path><glyph.data ascent="3473" descent="-2876" horiz-adv-x="480" vert-adv-y="480"></glyph.data></g></svg> compared with HG group treated with vehicle or transfected with scramble shRNA.</div>

Journal of Diabetes Research

fig7

Figure 7

Figure 7: NADPH Oxidase-Induced NALP3 Inflammasome Activation Is Driven by Thioredoxin-Interacting Protein Which Contributes to Podocyte Injury in Hyperglycemia 

Figure 7 | NADPH Oxidase-Induced NALP3 Inflammasome Activation Is Driven by Thioredoxin-Interacting Protein Which Contributes to Podocyte Injury in Hyperglycemia 