The Overexpression of miR-377 Aggravates Sepsis-Induced Myocardial Hypertrophy by Binding to Rcan2 and Mediating CaN Activity

<div>MiR-377 repression could ameliorate cardiomyocyte hypertrophy in septic mice induced by CLP. (a) LVPW, LVESD, EF, and FS detected by echocardiography and HW and LVW/BW measured by weighing, reflecting the successful establishment of a sepsis mouse model, wherein the sepsis was induced by CLP. (b) Myocardial damage of mice in each group, as detected by HE staining. (c) Myocardial tissue morphology of mice in each group, as observed by transmission electron microscope. (d) The expression of inflammatory factors in myocardial tissues of mice, as evaluated by ELISA assay. <svg height="13.532pt" id="M26" style="vertical-align:-3.4295pt" version="1.1" viewbox="-0.0498162 -10.1025 50.6052 13.532" width="50.6052pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.0091,0,0,-0.0091,0,-5.741)"><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"></path></g><g transform="matrix(.013,0,0,-0.013,6.079,0)"><path d="M570 304C570 398 525 448 414 448C385 448 343 445 312 434L329 511L321 518C297 504 262 482 244 460L233 411C195 397 159 381 128 358L135 332C160 347 189 360 224 373L111 -147C97 -210 84 -218 17 -231L13 -257L254 -247L259 -218L233 -216C183 -212 177 -202 189 -142L218 -1C238 -10 266 -12 283 -12C351 3 429 48 483 105C543 168 570 242 570 304ZM482 289C482 161 380 33 304 33C278 33 248 51 233 69L303 396C326 400 352 403 369 403C428 403 482 380 482 289Z"></path></g><g transform="matrix(.013,0,0,-0.013,17.421,0)"><path d="M512 -3V55L134 254V256L512 456V514L75 281V230L512 -3Z"></path></g><g transform="matrix(.013,0,0,-0.013,28.684,0)"><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"></path></g><g transform="matrix(.013,0,0,-0.013,34.924,0)"><path d="M113 -12C146 -12 170 11 170 46C170 78 146 103 114 103S58 78 58 46C58 11 82 -12 113 -12Z"></path></g><g transform="matrix(.013,0,0,-0.013,37.888,0)"><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"></path></g><g transform="matrix(.013,0,0,-0.013,44.128,0)"><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"></path></g></svg> compared with sham-operated mice. #<svg height="11.7782pt" id="M27" style="vertical-align:-3.42938pt" version="1.1" viewbox="-0.0498162 -8.34882 44.5261 11.7782" width="44.5261pt" 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="M570 304C570 398 525 448 414 448C385 448 343 445 312 434L329 511L321 518C297 504 262 482 244 460L233 411C195 397 159 381 128 358L135 332C160 347 189 360 224 373L111 -147C97 -210 84 -218 17 -231L13 -257L254 -247L259 -218L233 -216C183 -212 177 -202 189 -142L218 -1C238 -10 266 -12 283 -12C351 3 429 48 483 105C543 168 570 242 570 304ZM482 289C482 161 380 33 304 33C278 33 248 51 233 69L303 396C326 400 352 403 369 403C428 403 482 380 482 289Z"></path></g><g transform="matrix(.013,0,0,-0.013,11.342,0)"><path d="M512 -3V55L134 254V256L512 456V514L75 281V230L512 -3Z"></path></g><g transform="matrix(.013,0,0,-0.013,22.605,0)"><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"></path></g><g transform="matrix(.013,0,0,-0.013,28.845,0)"><path d="M113 -12C146 -12 170 11 170 46C170 78 146 103 114 103S58 78 58 46C58 11 82 -12 113 -12Z"></path></g><g transform="matrix(.013,0,0,-0.013,31.809,0)"><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"></path></g><g transform="matrix(.013,0,0,-0.013,38.049,0)"><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"></path></g></svg> compared with the antagomir NC group. &amp;<svg height="11.7782pt" id="M28" style="vertical-align:-3.42938pt" version="1.1" viewbox="-0.0498162 -8.34882 44.5261 11.7782" width="44.5261pt" 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="M570 304C570 398 525 448 414 448C385 448 343 445 312 434L329 511L321 518C297 504 262 482 244 460L233 411C195 397 159 381 128 358L135 332C160 347 189 360 224 373L111 -147C97 -210 84 -218 17 -231L13 -257L254 -247L259 -218L233 -216C183 -212 177 -202 189 -142L218 -1C238 -10 266 -12 283 -12C351 3 429 48 483 105C543 168 570 242 570 304ZM482 289C482 161 380 33 304 33C278 33 248 51 233 69L303 396C326 400 352 403 369 403C428 403 482 380 482 289Z"></path></g><g transform="matrix(.013,0,0,-0.013,11.342,0)"><path d="M512 -3V55L134 254V256L512 456V514L75 281V230L512 -3Z"></path></g><g transform="matrix(.013,0,0,-0.013,22.605,0)"><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"></path></g><g transform="matrix(.013,0,0,-0.013,28.845,0)"><path d="M113 -12C146 -12 170 11 170 46C170 78 146 103 114 103S58 78 58 46C58 11 82 -12 113 -12Z"></path></g><g transform="matrix(.013,0,0,-0.013,31.809,0)"><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"></path></g><g transform="matrix(.013,0,0,-0.013,38.049,0)"><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"></path></g></svg> compared with the antagomir NC group. Measurement data were represented as <span class="nowrap"><svg height="9.63826pt" id="M29" style="vertical-align:-0.3499298pt" version="1.1" viewbox="-0.0498162 -9.28833 143.44 9.63826" width="143.44pt" 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="M766 88L752 113C719 83 690 64 681 64C674 64 672 74 679 103L724 292C758 436 724 448 701 448C680 448 666 442 639 429C594 407 514 350 441 252H439L447 289C476 423 450 448 419 448C398 448 379 441 355 427C307 400 234 344 162 249H160L180 324C203 409 197 448 170 448C144 448 82 413 23 349L35 321C57 343 96 374 108 374C115 374 117 371 111 341C87 227 57 112 24 -6L32 -12C53 -4 81 4 108 6C119 68 134 128 149 171C177 229 309 383 364 383C387 383 388 355 373 282C354 190 330 92 303 -6L309 -12C332 -4 356 3 386 6C396 63 411 122 424 171C458 236 590 383 642 383C658 383 664 369 652 315L603 91C587 20 593 -12 619 -12C642 -12 708 23 766 88Z"></path></g><g transform="matrix(.013,0,0,-0.013,10.257,0)"><path d="M391 364C391 409 353 448 295 448C249 448 198 426 152 393C65 331 23 225 23 139C23 14 96 -12 146 -12C198 -12 280 9 367 101L351 124C300 78 242 48 194 48C129 48 109 107 109 162V191C208 213 391 266 391 364ZM313 350C313 305 268 261 113 223C132 334 187 381 217 398C227 404 244 405 261 405C290 405 313 385 313 350Z"></path></g><g transform="matrix(.013,0,0,-0.013,15.64,0)"><path d="M483 97L471 123C436 91 401 65 392 65C388 65 384 74 390 106C414 239 444 378 457 429L455 433C444 433 429 436 416 439C392 444 368 448 344 448C281 448 204 415 152 376C71 315 23 205 23 103C23 21 57 -12 85 -12C114 -12 149 6 185 34C231 70 285 119 329 183H331L309 81C292 0 308 -12 326 -12C350 -12 421 24 483 97ZM374 387C370 363 356 291 345 261C315 193 181 50 139 50C124 50 110 71 110 118C110 224 153 331 218 379C238 394 271 402 301 402C329 402 359 394 374 387Z"></path></g><g transform="matrix(.013,0,0,-0.013,22.22,0)"><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"></path></g><g transform="matrix(.013,0,0,-0.013,31.651,0)"><path d="M535 290V340H323V533H265V340H52V290H265V84H323V290H535ZM535 -22V28H52V-22H535Z"></path></g><g transform="matrix(.013,0,0,-0.013,42.188,0)"><path d="M352 391C352 416 319 448 267 448C236 448 173 423 147 400C107 364 96 332 96 304C96 248 143 210 193 181C241 153 258 124 258 100C258 72 232 38 184 38C151 38 107 66 81 108C77 114 64 116 55 111C34 99 23 84 23 65C23 29 81 -12 134 -12C220 -12 325 61 325 141C325 184 297 215 234 256C194 282 161 309 161 346C161 380 188 401 217 401C255 401 279 380 301 353C308 344 313 341 325 347C341 355 352 371 352 391Z"></path></g><g transform="matrix(.013,0,0,-0.013,47.324,0)"><path d="M324 430H196L233 583L223 592L145 529L120 430H54L29 396L31 388H111L56 126C33 15 54 -12 77 -12C137 -12 214 57 250 95L233 119C208 92 155 59 138 59C126 59 120 70 131 125L186 390L298 394L324 430Z"></path></g><g transform="matrix(.013,0,0,-0.013,51.757,0)"><path d="M483 97L471 123C436 91 401 65 392 65C388 65 384 74 390 106C414 239 444 378 457 429L455 433C444 433 429 436 416 439C392 444 368 448 344 448C281 448 204 415 152 376C71 315 23 205 23 103C23 21 57 -12 85 -12C114 -12 149 6 185 34C231 70 285 119 329 183H331L309 81C292 0 308 -12 326 -12C350 -12 421 24 483 97ZM374 387C370 363 356 291 345 261C315 193 181 50 139 50C124 50 110 71 110 118C110 224 153 331 218 379C238 394 271 402 301 402C329 402 359 394 374 387Z"></path></g><g transform="matrix(.013,0,0,-0.013,58.338,0)"><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"></path></g><g transform="matrix(.013,0,0,-0.013,64.864,0)"><path d="M530 686C535 705 530 712 521 712C504 712 448 684 359 674L358 648H393C437 648 439 646 429 593L400 435C372 447 345 448 332 448C286 448 194 414 144 373C68 311 23 203 23 111C23 26 57 -12 91 -12C120 -12 147 3 188 29C227 54 290 102 341 170H343L322 71C308 6 320 -12 341 -12C373 -12 442 27 501 96L485 120C455 91 422 67 408 67C401 67 401 76 404 91C440 294 479 473 530 686ZM387 375L355 241C326 187 200 53 142 53C126 53 109 73 109 130C109 217 154 337 218 381C240 396 265 404 297 404S372 390 387 375Z"></path></g><g transform="matrix(.013,0,0,-0.013,72.079,0)"><path d="M483 97L471 123C436 91 401 65 392 65C388 65 384 74 390 106C414 239 444 378 457 429L455 433C444 433 429 436 416 439C392 444 368 448 344 448C281 448 204 415 152 376C71 315 23 205 23 103C23 21 57 -12 85 -12C114 -12 149 6 185 34C231 70 285 119 329 183H331L309 81C292 0 308 -12 326 -12C350 -12 421 24 483 97ZM374 387C370 363 356 291 345 261C315 193 181 50 139 50C124 50 110 71 110 118C110 224 153 331 218 379C238 394 271 402 301 402C329 402 359 394 374 387Z"></path></g><g transform="matrix(.013,0,0,-0.013,78.659,0)"><path d="M393 379C402 394 400 411 393 422C384 437 365 448 348 448C301 448 237 372 186 285H182L193 335C210 408 205 448 178 448C150 448 80 402 29 344L45 321C80 355 114 373 122 373C128 373 130 365 124 330C106 228 76 98 50 -5L57 -12C82 -5 112 3 132 6L172 203C196 256 234 304 254 329C275 355 293 367 306 367C318 367 330 360 342 348C347 343 355 343 365 350S386 367 393 379Z"></path></g><g transform="matrix(.013,0,0,-0.013,84.147,0)"><path d="M530 686C535 705 530 712 521 712C504 712 448 684 359 674L358 648H393C437 648 439 646 429 593L400 435C372 447 345 448 332 448C286 448 194 414 144 373C68 311 23 203 23 111C23 26 57 -12 91 -12C120 -12 147 3 188 29C227 54 290 102 341 170H343L322 71C308 6 320 -12 341 -12C373 -12 442 27 501 96L485 120C455 91 422 67 408 67C401 67 401 76 404 91C440 294 479 473 530 686ZM387 375L355 241C326 187 200 53 142 53C126 53 109 73 109 130C109 217 154 337 218 381C240 396 265 404 297 404S372 390 387 375Z"></path></g><g transform="matrix(.013,0,0,-0.013,93.538,0)"><path d="M530 686C535 705 530 712 521 712C504 712 448 684 359 674L358 648H393C437 648 439 646 429 593L400 435C372 447 345 448 332 448C286 448 194 414 144 373C68 311 23 203 23 111C23 26 57 -12 91 -12C120 -12 147 3 188 29C227 54 290 102 341 170H343L322 71C308 6 320 -12 341 -12C373 -12 442 27 501 96L485 120C455 91 422 67 408 67C401 67 401 76 404 91C440 294 479 473 530 686ZM387 375L355 241C326 187 200 53 142 53C126 53 109 73 109 130C109 217 154 337 218 381C240 396 265 404 297 404S372 390 387 375Z"></path></g><g transform="matrix(.013,0,0,-0.013,100.753,0)"><path d="M391 364C391 409 353 448 295 448C249 448 198 426 152 393C65 331 23 225 23 139C23 14 96 -12 146 -12C198 -12 280 9 367 101L351 124C300 78 242 48 194 48C129 48 109 107 109 162V191C208 213 391 266 391 364ZM313 350C313 305 268 261 113 223C132 334 187 381 217 398C227 404 244 405 261 405C290 405 313 385 313 350Z"></path></g><g transform="matrix(.013,0,0,-0.013,106.135,0)"><path d="M219 86C216 168 211 250 206 337C201 410 189 448 163 448C131 448 79 396 43 344L60 322C91 359 110 375 118 375S132 358 136 298C141 238 152 81 155 -12H182C242 62 331 177 390 258C435 321 451 360 451 391C450 424 432 448 408 448C390 448 372 435 366 419C362 410 362 401 366 394C373 383 376 367 376 350C376 283 262 138 221 86H219Z"></path></g><g transform="matrix(.013,0,0,-0.013,111.999,0)"><path d="M244 607C244 633 228 655 200 655C166 655 146 618 146 594C146 564 166 546 191 546C221 546 244 574 244 607ZM222 91L209 114C184 94 148 66 133 66C127 66 124 73 130 96L201 370C213 416 211 448 191 448C162 448 88 407 29 352L42 328C73 354 104 371 114 371C120 371 119 365 115 345L53 92C32 5 45 -12 68 -12C103 -12 186 50 222 91Z"></path></g><g transform="matrix(.013,0,0,-0.013,115.548,0)"><path d="M483 97L471 123C436 91 401 65 392 65C388 65 384 74 390 106C414 239 444 378 457 429L455 433C444 433 429 436 416 439C392 444 368 448 344 448C281 448 204 415 152 376C71 315 23 205 23 103C23 21 57 -12 85 -12C114 -12 149 6 185 34C231 70 285 119 329 183H331L309 81C292 0 308 -12 326 -12C350 -12 421 24 483 97ZM374 387C370 363 356 291 345 261C315 193 181 50 139 50C124 50 110 71 110 118C110 224 153 331 218 379C238 394 271 402 301 402C329 402 359 394 374 387Z"></path></g><g transform="matrix(.013,0,0,-0.013,122.128,0)"><path d="M324 430H196L233 583L223 592L145 529L120 430H54L29 396L31 388H111L56 126C33 15 54 -12 77 -12C137 -12 214 57 250 95L233 119C208 92 155 59 138 59C126 59 120 70 131 125L186 390L298 394L324 430Z"></path></g><g transform="matrix(.013,0,0,-0.013,126.692,0)"><path d="M244 607C244 633 228 655 200 655C166 655 146 618 146 594C146 564 166 546 191 546C221 546 244 574 244 607ZM222 91L209 114C184 94 148 66 133 66C127 66 124 73 130 96L201 370C213 416 211 448 191 448C162 448 88 407 29 352L42 328C73 354 104 371 114 371C120 371 119 365 115 345L53 92C32 5 45 -12 68 -12C103 -12 186 50 222 91Z"></path></g><g transform="matrix(.013,0,0,-0.013,130.241,0)"><path d="M445 282C445 390 384 448 297 448C266 448 231 437 189 418C96 376 23 279 23 151C23 65 66 -12 169 -12C233 -12 294 18 337 53C411 113 445 201 445 282ZM355 280C355 161 302 62 243 36C231 31 219 30 207 30C147 30 111 78 111 154C111 302 180 380 220 399C231 404 246 407 264 407C311 407 355 367 355 280Z"></path></g><g transform="matrix(.013,0,0,-0.013,136.325,0)"><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"></path></g></svg>.</span> One-way ANOVA with Tukey’s posthoc test was employed to analyze data of multiple groups. <span class="nowrap"><svg height="8.55521pt" id="M30" style="vertical-align:-0.2063904pt" version="1.1" viewbox="-0.0498162 -8.34882 27.8368 8.55521" width="27.8368pt" 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="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"></path></g><g transform="matrix(.013,0,0,-0.013,10.158,0)"><path d="M535 323V373H52V323H535ZM535 138V188H52V138H535Z"></path></g><g transform="matrix(.013,0,0,-0.013,21.421,0)"><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"></path></g></svg>,</span> mice in each group.</div>

Oxidative Medicine and Cellular Longevity

fig2

Figure 2

Figure 2: The Overexpression of miR-377 Aggravates Sepsis-Induced Myocardial Hypertrophy by Binding to Rcan2 and Mediating CaN Activity 