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4.13:

์„ธํฌ์™ธ ๊ธฐ์งˆ

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JoVE Core Biology
The Extracellular Matrix

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– ๋งŽ์€ ์„ธํฌ ์กฐ์ง์„ ์ง€์ง€ํ•ด์ฃผ๋Š”์„ธํฌ์™ธ ๊ธฐ์งˆ๋˜๋Š” ECN๋Š”์ƒํ˜ธ ์—ฐ๊ฒฐ๋œ ๋„คํŠธ์›Œํฌ๋กœ์„œ์„ฌ์œ ์™€ ๋ฐ”ํƒ• ๋ฌผ์งˆ๋กœ ๊ตฌ์„ฑ๋˜์–ด ์žˆ์œผ๋ฉฐ์ด์˜ ๋Œ€๋ถ€๋ถ„์€ ๊ฐ„์งˆ ์œ ์ฒด๋กœ์„œ์„ธํฌ ์‚ฌ์ด ๊ณต๊ฐ„์„ ๋ฉ”๊พธ๋Š”๋ฐ, ์ด๋Š” ๊ฒฐํ•ฉ ์กฐ์ง ์„ฌ์œ ์™€๋ชจ์„ธ ํ˜ˆ๊ด€์ž…๋‹ˆ๋‹ค๊ฐ ๋ฏธ์„ธ ํ™˜๊ฒฝ์˜ ๋ถ„์ž ๊ตฌ์„ฑ์€๊ตญ๋ถ€ ์„ธํฌ์— ์˜ํ•ด ๋ถ„๋น„๋˜๋ฉฐ์„ฌ์œ ์•„ ์„ธํฌ์—์„œ ๋Œ€์‹ ์„ธํฌ์— ์ด๋ฅด๋ฉฐ์ฐจ์ด๊ฐ€ ์ •ํ™•ํ•œ ๊ตฌ์„ฑ๊ณผ๋ฌผ๋ฆฌ์  ํŠน์„ฑ์— ๋‚˜ํƒ€๋‚˜๊ฒŒ ๋ฉ๋‹ˆ๋‹ค์˜ˆ๋ฅผ ๋“ค์–ด, ๊ธฐ์งˆ์„ ์ฑ„์šฐ๊ณ  ์žˆ๋Š” ๊ฒƒ์€ ์ค‘ํ•ฉ๋œ๊ธ€๋ฆฌ์ฝ”์•„๋ฏธ๋…ธ๊ธ€๋ฆฌ์นธ๋˜๋Š” GAG ์ž…๋‹ˆ๋‹ค์ด๋“ค์ด ๋ฌผ๊ณผ ๋‹ค๋ฅธ ๋‹จ๋ฐฑ์งˆ์„ ๊ฒฐํ•ฉํ•˜๊ณ ํ”„๋กœํ…Œ์˜ค๊ธ€๋ฆฌ์นธ์ด ํ˜•์„ฑ๋ฉ๋‹ˆ๋‹ค๊ฐ€์žฅ ์ผ๋ฐ˜์ ์ธ ์ฝ˜๋“œ๋กœ์ดํ‹ด ํ™ฉ์‚ฐ์—ผ์€์—ฐ๊ณจ๊ณผ ๋ผˆ์— ํ•„์ˆ˜์ ์ด๋ฉฐ์ ์ง„์ ์ธ ์†์‹ค์€ ๋ฌด๋ฆŽ ๊ด€์ ˆ์—ผ์„ ์œ ๋ฐœํ•ฉ๋‹ˆ๋‹ค์—˜๋ผ์Šคํ‹ด์ด๋ผ๋Š” ๋˜ ๋‹ค๋ฅธ ๋‹จ๋ฐฑ์งˆ์€ ์‹ ์ถ•์„ฑ์— ๊ธฐ์—ฌํ•˜์—ฌ๊ทผ์œก๊ณผ ํ”ผ๋ถ€๊ฐ€ ์œ ์—ฐํ•ด์ง‘๋‹ˆ๋‹ค๋ฐ˜๋ฉด, ๋‹จ๋‹จํ•จ์˜ ์ œ๊ณต์€ ๊ธธ๊ณ  ๋‘๊บผ์šด ์„ฌ์œ ๋กœ ๋œ๋‹น๋‹จ๋ฐฑ์œผ๋กœ ์ฝœ๋ผ๊ฒ์ด๋ผ๊ณ  ํ•ฉ๋‹ˆ๋‹ค๋งค์šฐ ํ”ํ•˜์ง€๋งŒ, ํŠนํžˆ ์ด๋ฅผ ์ค‘์š”์‹œํ•˜๋Š” ๋Œ€์ƒ์€ํž˜์ค„๊ณผ ๊ฐ™์ด ๊ฐ•ํ•˜๊ณ  ๋งค์šฐ ๊ฑฐ์นœ ์กฐ์ง์œผ๋กœ๊ทผ์œก๊ณผ ๋ผˆ๋ฅผ ์—ฐ๊ฒฐํ•ฉ๋‹ˆ๋‹ค์ ‘์ฐฉ ์—ญํ• ์€ ํŒŒ์ด๋ธŒ๋กœ๋„ฅํ‹ด์ธ ์„ธํฌ ์ ‘์ฐฉ ๋‹จ๋ฐฑ์งˆ์ด๋ฉฐ์„ธํฌ๋ฅผ ๋‹ฌ๋ผ๋ถ™๊ฒŒ ํ•˜์—ฌ๋‹ค๋ฅธ ๊ธฐ์งˆ ์š”์†Œ์— ๋ถ€์ฐฉ๋˜๋Š”๋ฐ, ์ฝœ๋ผ๊ฒ๊ณผGAG ๋ฐ ์ธํ…Œ๊ทธ๋ฆฐ์ด ํฌํ•ฉ๋ฉ๋‹ˆ๋‹ค๋ง‰ ๋‹จ๋ฐฑ์งˆ์€ ์„ธํฌ๋ฅผ ๊ทธ ํ™˜๊ฒฝ์— ์—ฐ๊ฒฐ์‹œ์ผœ์ฃผ๋ฉฐ์‹ ํ˜ธ์ „๋‹ฌ ์บ์Šค์ผ€์ด๋“œ์—์„œ ์ค‘์š”ํ•œ ์—ญํ• ์„ ํ•ฉ๋‹ˆ๋‹ค๊ถ๊ทน์ ์œผ๋กœ, ์–ด๋””์— ์œ„์น˜ํ•ด ์žˆ๋”๋ผ๋„ECN์€ ์„œํฌํŠธ ๋„คํŠธ์›Œํฌ๋ฅผ ์•„์šฐ๋ฅด๋ฉฐ์ด๋Š” ์„ธํฌ์™€ ์กฐ์ง ์ฃผ๋ณ€์˜ ํ†ตํ•ฉ์— ํ•„์š”ํ•œ ๊ฒƒ์ž…๋‹ˆ๋‹ค

4.13:

์„ธํฌ์™ธ ๊ธฐ์งˆ

๊ฐœ์š”

์ƒ์ฒด์กฐ์ง(tissue)์˜ ์กฐ์ง(organization)์„ ์œ ์ง€ํ•˜๊ธฐ ์œ„ํ•ด ์—ฌ๋Ÿฌ ๋™๋ฌผ ์„ธํฌ๋Š” ์„ธํฌ์™ธ ๊ธฐ์งˆ(extracellular matrix, ์ค„์—ฌ์„œ ECM)์„ ๊ตฌ์„ฑํ•˜๋Š” ๊ตฌ์กฐ์ ์ธ ๋ถ„์ž์— ๋‘˜๋Ÿฌ์‹ธ์—ฌ ์žˆ์Šต๋‹ˆ๋‹ค. ECM์— ์žˆ๋Š” ๋ถ„์ž๋Š” ์กฐ์ง์˜ ๊ตฌ์กฐ์  ์˜จ์ „ํ•จ์„ ์œ ์ง€ํ•˜๊ณ  ํŠน์ • ์กฐ์ง์˜ ๋†€๋ผ์šด ํŠน์„ฑ๋„ ์œ ์ง€ํ•ฉ๋‹ˆ๋‹ค.

์„ธํฌ์™ธ ๊ธฐ์งˆ์˜ ๊ตฌ์„ฑ

์„ธํฌ์™ธ ๊ธฐ์งˆ(์ดํ•˜ ECM)์€ ์ผ๋ฐ˜์ ์œผ๋กœ ์ ‘์ง€ ๋ฌผ์งˆ(ground substance), ์ ค๊ณผ ๊ฐ™์€ ์•ก์ฒด, ์„ฌ์œ  ์„ฑ๋ถ„, ๊ทธ๋ฆฌ๊ณ  ์—ฌ๋Ÿฌ ๊ตฌ์กฐ์ , ๊ธฐ๋Šฅ์ ์œผ๋กœ ๋‹ค์–‘ํ•œ ๋ถ„์ž๋กœ ๊ตฌ์„ฑ๋˜๋Š”๋ฐ, ์—ฌ๊ธฐ์„œ ์ด ๋ถ„์ž๋Š” ๊ธ€๋ฆฌ์ฝ”์‚ฌ๋ฏธ๋…ธ๊ธ€๋ฆฌ์นธ(glycosaminoglycan, ์ค„์—ฌ์„œ GAG. ์ดํ•˜ GAG๋ผ ์นญํ•จ)์ด๋ผ ๋ถˆ๋ฆฌ๋Š” ๋‹ค๋‹น๋ฅ˜(polysaccharide)๋ฅผ ํฌํ•จํ•ฉ๋‹ˆ๋‹ค. GAG๋Š” ์„ธํฌ์™ธ ๊ธฐ์งˆ์˜ ๋Œ€๋ถ€๋ถ„์„ ์ฐจ์ง€ํ•˜๊ณ  ์ข…์ข… ์งˆ๋Ÿ‰์— ๋น„ํ•ด ํฐ ๋ถ€ํ”ผ๋ฅผ ์ฐจ์ง€ํ•˜๋Š”๋ฐ ์ด๋กœ ์ธํ•ด ์—„์ฒญ๋‚œ ์••์ถ•๋ ฅ์„ ๊ฒฌ๋”œ ์ˆ˜ ์žˆ๋Š” ๊ธฐ์งˆ(matrix)์ด ๋ฐœ์ƒํ•ฉ๋‹ˆ๋‹ค. ๋Œ€๋ถ€๋ถ„์˜ GAG๋Š” ๋‹จ๋ฐฑ์งˆ์— ๊ฒฐํ•ฉํ•ด ํ”„๋กœํ…Œ์˜ค๊ธ€๋ฆฌ์นธ(proteoglycans)์„ ๋งŒ๋“œ๋Š”๋ฐ ํ•ด๋‹น๋ถ„์ž๋Š” ๋ถ„์ž ์ž์‹ ์˜ ์–‘์ „ํ•˜์— ๋”ฐ๋ผ ๋‚˜ํŠธ๋ฅจ ์ด์˜จ์„ ๊ฐ„์งํ•ด ๋ฌผ์„ ๋Œ์–ด๋“ค์ด๊ฒŒ ๋˜์–ด ECM์— ์ˆ˜๋ถ„์„ ๊ณต๊ธ‰ํ•ฉ๋‹ˆ๋‹ค.

ECM์€ ๋˜ํ•œ ECM์˜ ๊ธฐ๋ณธ ๋‹จ๋ฐฑ์งˆ ๊ตฌ์„ฑ์š”์†Œ์ธ ์ฝœ๋ผ๊ฒ(collagen) ๊ฐ™์ด ๋‹จ๋‹จํ•œ ์„ฌ์œ ๋ฅผ ํฌํ•จํ•ฉ๋‹ˆ๋‹ค. ์ฝœ๋ผ๊ฒ์€ ๋™๋ฌผ์—๊ฒŒ ์žˆ๋Š” ๊ฐ€์žฅ ํ’๋ถ€ํ•œ ๋‹จ๋ฐฑ์งˆ๋กœ ์งˆ๋Ÿ‰ ๊ธฐ์ค€ ๋‹จ๋ฐฑ์งˆ์˜ 25%๋ฅผ ์ฐจ์ง€ํ•ฉ๋‹ˆ๋‹ค. ๊ตฌ์กฐ์ ์œผ๋กœ ์œ ์‚ฌํ•œ ๋‹ค์–‘ํ•œ ์ฝœ๋ผ๊ฒ์€ ์—ฌ๋Ÿฌ ์กฐ์ง์— ์ธ์žฅ ๊ฐ•๋„(tensile strength)๋ฅผ ๋ถ€์—ฌํ•ฉ๋‹ˆ๋‹ค.

ํŠนํžˆ, ํ”ผ๋ถ€, ํ˜ˆ๊ด€, ํ์™€ ๊ฐ™์€ ์กฐ์ง์€ ์ƒ๋ฆฌ์ ์ธ ์—ญํ• ์„ ์ˆ˜ํ–‰ํ•˜๊ธฐ ์œ„ํ•ด ๊ฐ•ํ•˜๊ณ  ์‹ ์ถ•์„ฑ์ด ์žˆ์–ด์•ผ ํ•ฉ๋‹ˆ๋‹ค. ์—˜๋ผ์Šคํ‹ด(elastin)์ด๋ผ๊ณ  ๋ถˆ๋ฆฌ๋Š” ๋‹จ๋ฐฑ์งˆ์€ ํŠน์ • ์„ฌ์œ ์งˆ์— ๋Š˜์–ด์ง€๊ณ  ์ˆ˜์ถ•ํ•˜๋Š” ๋Šฅ๋ ฅ์„ ๋ถ€์—ฌํ•ฉ๋‹ˆ๋‹ค. ํŒŒ์ด๋ธŒ๋กœ๋„ฅํ‹ด(fibronectin; ํ”ผ๋ธŒ๋กœ๋„ฅํ‹ด)์€ ์„ธํฌ๋ง‰์„ ํฌ๊ด„ํ•˜๋Š” ๋‹จ๋ฐฑ์งˆ (ํŠนํžˆ ์ธํ…Œ๊ทธ๋ฆฐ(integrin))์— ์ง์ ‘ ๊ฒฐํ•ฉํ•ด ECM๊ณผ ์„ธํฌ๋ง‰์„ ์—ฐ๊ฒฐํ•˜๊ธฐ ๋•Œ๋ฌธ์— ์„ธํฌ๋ถ€์ฐฉ(cell adhesion)์— ์ค‘์š”ํ•œ ๋‹น๋‹จ๋ฐฑ์งˆ(glycoprotein)์ž…๋‹ˆ๋‹ค. ์ธํ…Œ๊ทธ๋ฆฐ์€ ๋˜ํ•œ ์„ธํฌ ๋‚ด ๋ฐ˜์‘์„ ๋Œ์–ด๋‚ผ ์ˆ˜ ์žˆ๋Š” ์ฝœ๋ผ๊ฒ๊ณผ ์ƒํ˜ธ์ž‘์šฉํ•ฉ๋‹ˆ๋‹ค.

์„ธํฌ์™ธ ๊ธฐ์งˆ ๊ตฌ์„ฑ์€ ์กฐ์ง๊ณผ ์„ธํฌ ์œ ํ˜•์— ๋”ฐ๋ผ ๋‹ค๋ฆ…๋‹ˆ๋‹ค

ECM ๋‚ด๋ถ€ ๋ถ„์ž์˜ ๊ตฌ์„ฑ๊ณผ ์ƒ๋Œ€์  ๋น„์œจ์€ ์„ธํฌ๊ฐ€ ์žˆ๋Š” ์กฐ์ง(tissue)์˜ ์œ„์น˜, ์ƒ๋ฆฌํ•™์  ๊ธฐ๋Šฅ, ์ธ์ ‘ ์„ธํฌ ์œ ํ˜•์— ๋”ฐ๋ผ ๊ฒฐ์ •๋ฉ๋‹ˆ๋‹ค. ECM์˜ ์ด๋Ÿฌํ•œ ํŠน์ • ๋ถ„์ž ๊ตฌ์„ฑ์€ ๊ตญ์†Œ์  ๋ฏธ์„ธํ™˜๊ฒฝ(microenvironment)์ด๋ผ๊ณ  ํ•ฉ๋‹ˆ๋‹ค. ํŠน์ • ์กฐ์ง์˜ ์„ธํฌ๋Š” ์ฃผ๋ณ€ ECM์„ ๊ฒฐ์ •ํ•˜๋Š” ๋ถ„์ž๋ฅผ ๋ถ„๋น„ํ•ฉ๋‹ˆ๋‹ค. ์˜ˆ๋ฅผ ๋“ค์–ด, ์žฅ ์„ธํฌ๋Š” ์ž์‹ ์„ ๋‘˜๋Ÿฌ์‹ธ๊ณ  ์žˆ๋Š” ๊ธฐ์งˆ์— ํ•„์š”ํ•œ ๋ถ„์ž๋ฅผ ํ•ฉ์„ฑ, ์ˆ˜์ •, ๋ถ„๋น„ํ•˜๋Š” ๋ฐ˜๋ฉด, ๊ณจ ์„ธํฌ๋Š” ์ธ๊ฐ„ ๋ผˆ์— ๋‹จ๋‹จํ•จ์„ ๋ถ€์—ฌํ•˜๋Š” ECM ๋ถ„์ž๋ฅผ ์ƒ์„ฑํ•ฉ๋‹ˆ๋‹ค. ์ด๋ ‡๊ฒŒ ์—ฌ๋Ÿฌ ์กฐ์ง ๋‚ด ๋‹ค์–‘ํ•œ ECM ๊ตฌ์„ฑ์€ ์กฐ์ง์˜ ๋‹ค์–‘ํ•œ ์—ญํ• ๊ณผ ๊ธฐ๋Šฅ์— ๋”ฐ๋ฅธ ํŠน์„ฑ์„ ์ƒ์„ฑํ•ฉ๋‹ˆ๋‹ค.

์„ธํฌ์™ธ ๊ธฐ์งˆ์€ ์„ธํฌ ํ†ต์‹ ์— ๊ด€์—ฌ ํ•  ์ˆ˜ ์žˆ์Šต๋‹ˆ๋‹ค

์„ธํฌ์™€ ๊ตญ์†Œ ECM ๊ฐ„์˜ ์ƒํ˜ธ์ž‘์šฉ์ด ์„ธํฌ ๋‚ด ์˜ํ–ฅ์„ ๋ฏธ์น˜๋Š” ๊ฒƒ์€ ์•Œ๋ ค์ ธ ์žˆ์Šต๋‹ˆ๋‹ค. ์˜ˆ๋ฅผ ๋“ค์–ด, ๋ง‰์˜ ์•ˆํŒŽ์— ์žˆ๋Š” ์ธํ…Œ๊ทธ๋ฆฐ ๋ถ„์ž์— ์ž‘์šฉํ•˜๋Š” ํž˜์€ ์„ธํฌ ๋‚ด ์•กํ† ๋ฏธ์˜ค์‹ (actomyosin) ๋„คํŠธ์›Œํฌ์˜ ํ™œ์„ฑํ™”๋ฅผ ์ดˆ๋ž˜ํ•  ์ˆ˜ ์žˆ์Šต๋‹ˆ๋‹ค. ์ด๋Ÿฐ ํ˜„์ƒ์€ ์„ธํฌ ์ด๋™, ๋ถ„์—ด ๋ฐ ๊ธฐํƒ€ ์„ธํฌ ๋ฐ˜์‘์„ ์ด‰์ง„ํ•  ์ˆ˜ ์žˆ์Šต๋‹ˆ๋‹ค. ์ด๋Ÿฌํ•œ ์„ธํฌ๋ฐ˜์‘ ์ค‘ ์ผ๋ถ€๋Š” ์œ ์ „์ž ๋ฐœํ˜„(gene expression)๊ณผ ์„ธํฌ ์‹ ํ˜ธ์ „๋‹ฌ์ฒด๊ณ„์˜ ๋ณ€ํ™”๋ฅผ ํฌํ•จํ•ฉ๋‹ˆ๋‹ค. ๋งˆ์ฐฌ๊ฐ€์ง€๋กœ ์ธํ…Œ๊ทธ๋ฆฐ์€ ์„ธํฌ ๋‚ด ์ •๋ณด๋ฅผ ์„ธํฌ ์™ธ๋ถ€๋กœ ์ „๋‹ฌํ•  ์ˆ˜ ์žˆ์Šต๋‹ˆ๋‹ค. ๋˜ํ•œ ECM์€ ECM ๋ถ„ํ•ด ์‹œ ๋ฐฉ์ถœ๋  ์ˆ˜ ์žˆ๋Š” ์‹ ํ˜ธ ๋ถ„์ž์— ๊ฒฐํ•ฉํ•˜๋Š” ๊ฒƒ์œผ๋กœ ์•Œ๋ ค์ ธ ์žˆ์Šต๋‹ˆ๋‹ค.

์„ธํฌ์™ธ ๊ธฐ์งˆ์˜ ์žฌ๊ตฌ์„ฑ

๋™๋ฌผ ์„ธํฌ๋Š” ECM์„ ๋ถ„ํ•ดํ•˜๊ณ  ์žฌ๊ตฌ์„ฑํ•  ์ˆ˜ ์žˆ๋Š” ๋Šฅ๋ ฅ์ด ์žˆ์–ด์•ผ ํ•ฉ๋‹ˆ๋‹ค. ํŠนํžˆ ์กฐ์ง ์ˆ˜๋ณต(tissue repair)๊ณผ ์„ฑ์žฅ์˜ ๊ฒฝ์šฐ ์ด์— ํ•ด๋‹นํ•ฉ๋‹ˆ๋‹ค. ๋”ฐ๋ผ์„œ ์„ธํฌ๋Š” ์ผ๋ฐ˜์ ์œผ๋กœ ECM์„ ๋ถ„ํ•ดํ•˜๋Š” ๋ฐ ํ•„์š”ํ•œ ํšจ์†Œ๋ฅผ ๊ฐ€์ง€๊ณ  ์žˆ์Šต๋‹ˆ๋‹ค. ์ด๋Ÿฐ ํšจ์†Œ๋Š” ์ฝœ๋ผ๊ฒ๊ณผ ํŒŒ์ด๋ธŒ๋กœ๋„ฅํ‹ด๊ณผ ๊ฐ™์€ ๋‹จ๋ฐฑ์งˆ์„ ๋ถ„ํ•ดํ•˜๊ธฐ ์œ„ํ•ด ๋‹ค๋ฅธ ํšจ์†Œ์™€ ํ•จ๊ป˜ ์ž‘์šฉํ•˜๋Š” ๊ธฐ์งˆ ๊ธˆ์†๋‹จ๋ฐฑ์งˆ๋ถ„ํ•ดํšจ์†Œ(matrix metalloproteases, ์ค„์—ฌ์„œ MMP)๋ฅผ ํฌํ•จํ•ฉ๋‹ˆ๋‹ค. ECM ๋ถ„ํ•ด ๋ฐ ์žฌ๊ตฌ์„ฑ์€ ํ˜ˆ๊ด€ ์ƒ์„ฑ์„ ํฌํ•จ, ๊ฑด๊ฐ•ํ•œ ์กฐ์ง ์„ฑ์žฅ์— ์ค‘์š”ํ•ฉ๋‹ˆ๋‹ค. ๋‹จ์ ์€ ECM ์žฌ๊ตฌ์„ฑ์€ ์•”์„ธํฌ๊ฐ€ ์˜จ๋ชธ์œผ๋กœ ์ „์ดํ•˜๋Š”๋ฐ ์ด๋ฐ”์ง€ํ•˜๋Š” ์ ์ž…๋‹ˆ๋‹ค.

Suggested Reading

Frantz, Christian, Kathleen M. Stewart, and Valerie M. Weaver. “The Extracellular Matrix at a Glance.” Journal of Cell Science 123, no. 24 (December 15, 2010): 4195–4200. [Source]

Alberts, Bruce, Alexander Johnson, Julian Lewis, Martin Raff, Keith Roberts, and Peter Walter. “The Extracellular Matrix of Animals.” Molecular Biology of the Cell. 4th Edition, 2002. [Source]