Pamaso pa zotupa zam'mimba, ma cell ena oteteza thupi amaphwanya mapuloteni opangidwa kukhala mamolekyu omwe amayambitsa kupanga minofu yowuma, chotchinga chodziwika bwino chamankhwala, kafukufuku watsopano apeza.
Motsogozedwa ndi ofufuza ochokera ku NYU Grossman School of Medicine, kafukufukuyu akuzungulira ma meshwork a protein omwe amathandizira ziwalo ndikuthandizira kumanganso minofu yowonongeka. Mapuloteni a Collagen, chigawo chachikulu cha mauna, amaphwanyidwa mosalekeza ndikusinthidwa kuti akhalebe ndi mphamvu zolimba, komanso ngati gawo la kuchira kwa bala.
Kafukufuku wam'mbuyomu wasonyeza kuti maselo a chitetezo cha mthupi otchedwa macrophages amathandizira kupanga njira yotchedwa desmoplasia, yomwe imayamba chifukwa cha kutembenuka kwachilendo komanso kuyika kwambiri kwa kolajeni komwe kumateteza khansa ya kapamba. M'malo ano, ma macrophages amadziwikanso kuti amameza ndikuphwanya kolajeni kudzera m'mapuloteni otchedwa mannose receptor (MRC1).
Kusindikiza pa intaneti pa Epulo 4 mu Proceedings of the National Academies of Sciences, kafukufuku wapano adapeza kuti kolajeni yowonongeka idachulukitsa kuchuluka kwa arginine, amino acid yomwe imagwiritsidwa ntchito ndi enzyme nitric oxide synthase (iNOS) kupanga zinthu zomwe zimatchedwa reactive nitrogen mitundu. (RNS). Izi, zidapangitsa kuti maselo oyandikana nawo, othandizira a stellate apange ma meshes okhala ndi collagen kuzungulira zotupa, atero olemba kafukufukuyo.
"Zotsatira zathu zidawululira momwe zotupa za pancreatic macrophages zimathandizira pomanga zotchinga za fibrotic," akutero wolemba kafukufuku woyamba Madeleine LaRue, PhD. Pa nthawi ya phunziroli, LaRue anali wophunzira wophunzira mu labu la wolemba wamkulu wophunzirira Dafna Bar-Sagi, PhD, S. Farber Pulofesa wa Biochemistry ndi Molecular Pharmacology ndi Vice Dean for Science ku NYU Langone Health. "Maselo a maselowa atha kugwiritsidwa ntchito pothana ndi kusintha kwa khansa m'mapangidwe ozungulira zotupa," akuwonjezera LaRue.
Khansara ya Pancreatic ndi yachitatu yomwe imayambitsa kufa kwa khansa ku United States, ndikukhala ndi moyo zaka zisanu ndi 10%. Khansara ya kapamba imakhalabe yovuta kuchiza makamaka chifukwa cha kuchuluka kwa minofu ya fibrotic kuzungulira zotupa. Maukondewa samangoletsa mwayi wopezeka ndi mankhwala, komanso amalimbikitsa kukula kwaukali.
Pakafukufuku wapano, zoyeserera zidawonetsa kuti macrophages omwe amakula m'zakudya zopatsa thanzi (zikhalidwe), ndikusinthidwa kukhala malo awo osagwirizana ndi khansa (M2), adaphwanya kolajeni kwambiri kuposa macrophages omwe amalimbana ndi maselo a khansa (M1). Komanso, gululo linatsimikizira ndi mayesero angapo kuti M2 macrophages ali ndi ma enzyme apamwamba omwe amapanga RNS, monga iNOS.
Kuti atsimikizire zomwe zapezedwa mu mbewa zamoyo, gululo linaika maselo a stellate omwe "adadyetsedwa kale" ndi collage, kapena kusungidwa m'malo osadyetsedwa, m'mphepete mwa nyama zophunzira pamodzi ndi maselo a khansa ya pancreatic. Gululo lidawona kuwonjezeka kwa 100 peresenti kwa kachulukidwe ka intra-tumoral collagen fibers mu zotupa zochokera ku ma cell a khansa omwe adayikidwa ndi ma cell a stellate opangidwa kale ndi collagen.
Chofunika kwambiri, phunziroli linasonyeza kwa nthawi yoyamba kuti macrophages pafupi ndi maselo a khansa ya pancreatic, sikuti amangotenga ndikuphwanya collagen yambiri monga gawo la scavenging kwa mapuloteni omwe amadyetsa kukula kwachilendo, komanso amasinthidwa ndi scavenging, kotero kuti dongosolo lawo lokonzekera mphamvu. (metabolism) imalumikizidwanso ndi waya ndi chizindikiro cha kuchuluka kwa fibrotic.
"Gulu lathu lidavumbulutsa njira yomwe imagwirizanitsa kutembenuka kwa collagen ndikumanga malo osamva chithandizo mozungulira zotupa zam'mimba," akutero Bar-Sagi. "Popeza kuti malo owundanawa ndi chifukwa chachikulu chomwe khansa ya m'matumbo imapha kwambiri, kumvetsetsa bwino kugwirizana pakati pa kuwononga mapuloteni ndi kumanga zotchinga zoteteza kudzafunika kuti athe kuchiza matenda owopsawa."
