HYAL1 Is Downregulated in Idiopathic Pulmonary Fibrosis and Inhibits HFL-1 Fibroblast Proliferation When Upregulated

<div>Potential gene expression regulatory modes of <i>HYAL1</i>-overexpressed HFL-1 fibroblasts. (a) IPA clustering of classical signaling pathways that are regulated by all 1,664 genes with significantly altered expression profiles (<span class="nowrap"><svg height="9.16198pt" id="M114" style="vertical-align:-0.6370001pt" version="1.1" viewbox="-0.0498162 -8.52498 61.2677 9.16198" width="61.2677pt" 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="M493 503C489 551 484 614 483 650H43V622C120 616 128 611 128 525V126C128 40 120 34 40 28V0H312V28C221 34 213 40 213 126V307H316C407 307 412 296 424 227H453V420H424C412 355 407 346 316 346H213V584C213 613 216 616 246 616H322C398 616 419 607 436 579C449 559 455 539 464 499L493 503Z"></path></g><g transform="matrix(.013,0,0,-0.013,6.877,0)"><path d="M43 650V622C120 616 128 612 128 526V124C128 39 120 33 34 27V0H270C392 0 492 25 567 83C643 141 690 230 690 350C690 444 655 517 605 565C543 625 450 650 323 650H43ZM213 547C213 587 217 598 226 604C236 612 262 617 304 617C371 617 429 604 474 576C554 529 592 439 592 336C592 176 505 36 319 36C246 36 213 55 213 131V547Z"></path></g><g transform="matrix(.013,0,0,-0.013,16.315,0)"><path d="M631 18C609 24 585 35 559 65C534 91 514 117 478 169C448 214 406 281 389 313C462 346 516 399 516 485C516 545 490 590 449 616C412 641 363 650 290 650H42V622C120 615 128 612 128 527V125C128 40 120 34 38 28V0H300V28C221 34 212 40 212 125V284H244C295 284 312 272 329 244C359 195 395 133 430 84C475 19 516 -3 592 -7C603 -8 615 -8 627 -8L631 18ZM212 316V563C212 591 215 602 223 607C231 613 248 617 277 617C352 617 423 577 423 469C423 415 407 375 368 345C343 324 310 316 260 316H212Z"></path></g><g transform="matrix(.013,0,0,-0.013,28.111,0)"><path d="M512 -3V55L134 254V256L512 456V514L75 281V230L512 -3Z"></path></g><g transform="matrix(.013,0,0,-0.013,39.374,0)"><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,-0.013,45.614,0)"><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,-0.013,48.578,0)"><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,-0.013,54.818,0)"><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>;</span> Benjamini-Hochberg method) in <i>HYAL1</i>-overexpressed HFL-1 fibroblasts. Negative and positive <span class="nowrap"><svg height="9.01194pt" id="M115" style="vertical-align:-0.04981995pt" version="1.1" viewbox="-0.0498162 -8.96212 9.12937 9.01194" width="9.12937pt" 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="M669 636L663 650H260C230 650 221 652 208 675H186C177 621 162 548 144 481L173 479C195 534 211 560 226 578C248 604 266 615 373 615H544C460 511 114 112 23 16L31 0H561C577 34 611 135 622 170L594 182C566 125 544 88 515 65C481 38 416 35 319 35C249 35 197 37 152 41C270 184 542 501 669 636Z"></path></g></svg>-</span>scores are represented by blue and orange, respectively. A <svg height="9.59912pt" id="M116" style="vertical-align:-0.6370001pt" version="1.1" viewbox="-0.0498162 -8.96212 69.7494 9.59912" width="69.7494pt" 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="M669 636L663 650H260C230 650 221 652 208 675H186C177 621 162 548 144 481L173 479C195 534 211 560 226 578C248 604 266 615 373 615H544C460 511 114 112 23 16L31 0H561C577 34 611 135 622 170L594 182C566 125 544 88 515 65C481 38 416 35 319 35C249 35 197 37 152 41C270 184 542 501 669 636Z"></path></g><g transform="matrix(.013,0,0,-0.013,8.996,0)"><path d="M300 253H71L57 198H286L300 253Z"></path></g><g transform="matrix(.013,0,0,-0.013,13.642,0)"><path d="M319 325C317 349 306 409 297 431C277 440 250 449 209 449C117 449 57 389 57 319C57 243 122 209 182 182C232 159 261 135 261 91C261 48 227 21 190 21C130 21 85 79 68 145L41 140C41 104 51 36 58 22C75 7 121 -12 172 -12C252 -12 337 35 337 126C337 195 286 231 210 262C166 281 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140Z"></path></g></svg> indicates a strongly inhibited gene while a <svg height="9.59912pt" id="M117" style="vertical-align:-0.6370001pt" version="1.1" viewbox="-0.0498162 -8.96212 62.0898 9.59912" width="62.0898pt" 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="M669 636L663 650H260C230 650 221 652 208 675H186C177 621 162 548 144 481L173 479C195 534 211 560 226 578C248 604 266 615 373 615H544C460 511 114 112 23 16L31 0H561C577 34 611 135 622 170L594 182C566 125 544 88 515 65C481 38 416 35 319 35C249 35 197 37 152 41C270 184 542 501 669 636Z"></path></g><g transform="matrix(.013,0,0,-0.013,8.996,0)"><path d="M300 253H71L57 198H286L300 253Z"></path></g><g transform="matrix(.013,0,0,-0.013,13.642,0)"><path d="M319 325C317 349 306 409 297 431C277 440 250 449 209 449C117 449 57 389 57 319C57 243 122 209 182 182C232 159 261 135 261 91C261 48 227 21 190 21C130 21 85 79 68 145L41 140C41 104 51 36 58 22C75 7 121 -12 172 -12C252 -12 337 35 337 126C337 195 286 231 210 262C166 281 126 304 126 348C126 388 152 417 191 417C240 417 274 378 294 318L319 325Z"></path></g><g transform="matrix(.013,0,0,-0.013,18.517,0)"><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,-0.013,24.016,0)"><path d="M257 449C165 449 37 374 37 209C37 98 119 -12 256 -12C355 -12 473 65 473 226C473 349 381 449 257 449ZM244 416C333 416 380 320 380 204C380 67 329 21 267 21C184 21 130 115 130 241C130 354 184 416 244 416Z"></path></g><g transform="matrix(.013,0,0,-0.013,30.489,0)"><path d="M181 342V451C133 431 89 419 40 411V388C98 381 102 377 102 311V104C102 38 95 32 33 26V0H263V26C186 32 181 38 181 104V287C203 343 235 372 261 372C277 372 289 366 304 352C310 346 318 345 330 350C349 359 362 379 362 399C362 422 338 449 304 449C256 449 213 393 183 342H181Z"></path></g><g transform="matrix(.013,0,0,-0.013,35.143,0)"><path d="M380 106C343 72 306 56 265 56C195 56 116 112 115 248C235 252 361 262 377 265C396 269 400 277 400 297C400 374 333 449 250 449H249C198 449 144 421 103 376S37 269 37 201C37 88 109 -12 232 -12C263 -12 332 6 395 84L380 106ZM225 412C281 412 315 364 314 312C314 297 308 292 290 292C232 290 176 289 120 289C135 370 180 412 225 412Z"></path></g><g transform="matrix(.013,0,0,-0.013,44.402,0)"><path d="M512 230V281L75 514V456L453 256V254L75 55V-3L512 230Z"></path></g><g transform="matrix(.013,0,0,-0.013,55.665,0)"><path d="M412 140C382 77 369 73 315 73H129L270 222C362 320 402 379 402 466C402 571 322 635 234 635C177 635 130 609 99 576L42 495L64 475C90 514 133 568 201 568C274 568 318 519 318 435C318 349 255 267 193 193C144 135 87 78 32 23V0H405C417 45 427 89 440 131L412 140Z"></path></g></svg> indicates a strongly activated gene. (b) Genes with significantly altered expression levels (highlighted) along with other associated molecules are mapped to the classical osteoarthritis pathway. Upregulated and downregulated molecules are represented in red and green, respectively, and the different shades of color correspond to the different degree of regulation.</div>

BioMed Research International

fig7

Figure 7

Figure 7: HYAL1 Is Downregulated in Idiopathic Pulmonary Fibrosis and Inhibits HFL-1 Fibroblast Proliferation When Upregulated 