Brunton 1 (2018)

Kindler syndrome (KS), yotchedwa Kindler Syndrome (KS), yomwe idatchulidwa ndi dokotala yemwe adayifotokoza koyamba, ndi mtundu wa epidermolysis bullosa (EB) momwe khungu limakhala losalimba, limamva kuwala ndi matuza poyankha kuvulala. Munthu akamakalamba, khungu lawo limachepa, zomwe zimapangitsa kuti zisawonongeke. Odwala omwe ali ndi KS alinso pachiwopsezo chotenga khansa yapakhungu yotchedwa squamous cell carcinoma. KS imayamba chifukwa chotengera cholakwika mu jini yotchedwa KIND1 (kapena FERMT1) yomwe nthawi zambiri imayang'anira kupanga mapuloteni: Kindlin-1. Puloteni iyi ndi yofunika kwambiri pakugawanika kwa maselo (otchedwa mitosis) ndi kukula kwa maselo a khungu. Jini yolakwika imatulutsa puloteni ya Kindlin-1 yomwe siigwira bwino ntchito, zomwe zimapangitsa kuti khungu likhale lochepa thupi komanso losalimba. Komabe, momwe Kindlin-1 imathandizira kuti izi zitheke pamlingo wa mamolekyulu sizinamveke bwino. 

Zimamveka kuti Kindlin-1 ndi puloteni ya 'adaptor', zomwe zikutanthauza kuti imagwira ntchito pomanga mapuloteni ena muselo. Pulojekitiyi inkafuna kumvetsetsa momwe Kindlin-1 imagwirira ntchito ndi mapuloteni ena omwe amagawika ma cell. Gululi liri ndi njira zomwe zilipo mu labotale yawo zomwe zawathandiza kuzindikira kuti ndi mapuloteni ati omwe amalumikizana ndi wina ndi mzake komanso momwe mkati mwa selo zomwe zimagwirizanitsa zimachitika.

Maselo akhungu achibadwa amafananizidwa ndi omwe amachokera kwa anthu omwe ali ndi KS kuti adziwe masitepe a ma cell omwe sakugwira ntchito bwino pakhungu la KS. Gwirani ntchito kuti muwonjezere kumvetsetsa kwathu momwe Kindlin-1 imagwirira ntchito imathandizira kuti titha kupanga njira zomwe tingathandizire matendawa.

Kuyang'ana koyambirira kunawonetsa kuti kusowa kwa Kindlin-1 kunachepetsa kuchuluka kwa maselo omwe amatha kudutsa magawo a cell (mitosis) ndipo motero, kuchulukitsa, komwe kumatha chifukwa cha khungu lochepa thupi (la atrophic) lomwe limawoneka mwa odwala KS. Kufufuza kwinanso pakugawikana kwa ma cell kunawonetsa kuti Kindlin-1 imawongolera kukhazikika kwa microtubule. Ma microtubules amakhudzidwa ndi kusunga dongosolo la selo ndipo ndi gawo lalikulu la mitotic "spindle" ndipo amafunikira kuti alekanitse ma chromosome panthawi ya mitosis yomwe imalola maselo kugawanitsa bwino komanso moyenera. Spindle ya mitotic inali ndi mwayi wapamwamba wokhala wolakwika komanso wosakhazikika m'maselo opanda Kindlin-1. Kindlin-1 ndiyofunikira chifukwa imathandizira kuti pakhale bata pomanga ma microtubules, ofunikira kuti asunge kapangidwe ka cell ndi magawano a cell. Ku KS komwe khungu la odwala lilibe mtundu uliwonse wa Kindlin-1, kugawanika kwa maselo kumachepa, maselo ochepa omwe tikudziwa tsopano angayambitse khungu lochepa thupi kapena lopweteka.

Kuti mumvetse bwino zomwe mapuloteni ena a Kindlin-1 amamangiriza panthawi ya magawano a maselo; gulu lachita kafukufuku wokwanira. Atazindikira anzawo omwe amamangiriza a Kindlin-1, azindikira kuti Kindlin-1 imamangiriza kuwongolera kofunikira kwa ma cell otchedwa CDK. CDK imayang'anira kayendedwe ka ma cell kudzera mu cell cycle yomwe ndi njira yomwe maselo amagawikana.

Anapezanso kuti maselo a khungu la odwala omwe ali ndi KS amakhudzidwa kwambiri ndi kuwonongeka kwa Ultra Violet (UV). Kuwala kwa UV (kuwala kwa dzuwa) kumayambitsa kuwonongeka kwa DNA ndipo kumayambitsa maselo kufa ndipo Kindlin-1 imatha kuteteza maselo ku kuwonongeka kumeneku. Odwala a KS achulukitsa photosensitivity zomwe zikutanthauza kuti amakhudzidwa kwambiri ndi kuwala kwa UV. Zimaganiziridwa kuti Kindlin-1 imateteza khungu ku kuwonongeka kwa UV poyambitsa njira zopulumukira m'maselo. Njira zopulumutsirazi ndi mndandanda wolumikizana wa mapuloteni mkati mwa ma cell ndipo zochita zawo zimatumiza zizindikiro zopulumuka kumaselo. Gululi lazindikira puloteni imodzi yotere yotchedwa ERK yomwe ikukhudzidwa ndi njira yopulumukirayi pomwe ntchitoyo imayendetsedwa ndi Kindlin-1. 

Pomwe gululi laphunzira zambiri za ma cell omwe amakhudzidwa ndi KS, akuyenera kudziwa ngati, komanso bwanji, ena mwa mapuloteni kapena zolemberazi zimakhudza kufooka kwa khungu la KS. Gululi likuyembekeza kuti pozindikira mapuloteni kapena zolembera zomwe zimathandizira kukhazikika kwa ma cell kapena kukhala ndi moyo, izi zitha kutilola kuzindikira zomwe tikufuna kulandira mtsogolo.

Kindlin-1 amalumikizana ndi ma microtubules pa mitotic spindle - Mwachilolezo cha Pulofesa Brunton

"Kafukufuku wathu wapeza momwe Kindlin-1 imawongolera njira zofunika m'maselo omwe amawalola kukula komanso kudziteteza ku kuwonongeka kwa UV. Tsopano tikuyenera kumvetsetsa momwe tingabwezeretsere njirazi mwa anthu omwe ali ndi KS kuti apereke chithandizo chofunikira kwambiri. ”

Pulofesa Valerie Brunton

Pulofesa Valerie Brunton ndi Wapampando wa Cancer Therapeutics ku yunivesite ya Edinburgh. Zokonda zake ndikumvetsetsa biology ya Kindler Syndrome, atrophy yapakhungu (yofooka) ndi photosensitivity ndi chiopsezo chowonjezereka chokhala ndi khansa ya squamous cell. Kafukufuku wake akufuna kudziwa njira zazikulu zama cell zomwe zimayambitsa matenda a Kindler Syndrome kuti athandizire kuzindikira njira zochizira matendawa.