{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T11:16:24Z","timestamp":1784891784900,"version":"3.55.0"},"reference-count":57,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T00:00:00Z","timestamp":1765497600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Methusalem program of the Flemish Government","award":["METH\/14\/06"],"award-info":[{"award-number":["METH\/14\/06"]}]},{"name":"Research Foundation\u2014Flanders, Belgium","award":["G056521N"],"award-info":[{"award-number":["G056521N"]}]},{"name":"Research Foundation\u2014Flanders, Belgium","award":["G029525N"],"award-info":[{"award-number":["G029525N"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"\n Introduction<\/jats:title>\n \n Intensive-care-unit-acquired-muscle-weakness is a debilitating complication of sepsis, characterized by loss of muscle mass and functionality. Immobilization is an important trigger, but the role of disturbed mechanical signaling is incompletely understood. In health, the integrin-receptor-complex with key components Kindlin2 (KIND2\/\n Fermt2<\/jats:italic>\n ) and integrin-linked-kinase (ILK\/\n Ilk1<\/jats:italic>\n ) converses mechanical forces into biochemical signals to regulate muscle mass. We hypothesize that this complex, through key elements KIND2 and ILK, plays a role in sepsis-induced-muscle-weakness.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n AAV2\/9-vectors expressing shRNA-sequences against\n Ilk1, Fermt2<\/jats:italic>\n or noncoding-control-gene were injected in tibialis anterior (TA) muscles of 24w-old male C57BL\/6J mice. Two-weeks-post-injection, after knockdown validation, mice were made septic by cecal ligation and puncture. Five-days-post-sepsis muscle force, mass and fiber size were quantified and expression of mechanosensitive elements and downstream pathways of the integrin-receptor-complex was assessed.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Two-weeks-post-injection the respective sh-targets were strongly suppressed (mRNA\n Ilk1<\/jats:italic>\n \u201344%,\n Fermt2<\/jats:italic>\n \u201376%, protein ILK \u221234%, KIND2\u201370%). In rAAV-sh-\n controls<\/jats:italic>\n , sepsis induced upregulation across TA and EDL muscle of\n Ilk1<\/jats:italic>\n and\n Fermt2<\/jats:italic>\n and integrin-receptor-complex-related genes\n Itga<\/jats:italic>\n 7,\n ItgB1<\/jats:italic>\n ,\n Tln1<\/jats:italic>\n ,\n Lims1, Lims2, Parva<\/jats:italic>\n (\n P\u2009<\u20090.001<\/jats:italic>\n ), whereas in SOL muscle\n Lims1, Lims2<\/jats:italic>\n and\n Fermt2<\/jats:italic>\n were not and\n Vcl1<\/jats:italic>\n (\n P\u2009<\u20090.001<\/jats:italic>\n ) was upregulated. In TA and EDL, but not in SOL, rAAV-sh\n Ilk1<\/jats:italic>\n and rAAV-sh\n Fermt2<\/jats:italic>\n attenuated upregulation of respective targets down to healthy controls, but without affecting expression of other integrin-receptor-complex-related genes. TA muscle force or weight were not affected by rAAV-sh\n Ilk1<\/jats:italic>\n or rAAV-sh\n Fermt2<\/jats:italic>\n (\n P\u2009>\u20090.05<\/jats:italic>\n ), whereas muscle fiber size reduction (\u221220.7% in Sepsis shControl) was attenuated up to \u221213.4% (Sepsis sh\n Ilk1<\/jats:italic>\n ,\n P\u2009<\u20090.001<\/jats:italic>\n ) and \u221212.3% (Sepsis sh\n Fermt2<\/jats:italic>\n ,\n P\u2009<\u20090.001<\/jats:italic>\n ). Sepsis or sh-treatment did not shift TA fiber types. Expression of markers of atrophy, inflammation, autophagy, protein synthesis and regeneration were affected by sepsis, but not by sh-treatment. Only markers of metabolism\n Slc2a4<\/jats:italic>\n (\n P\u2009<\u20090.05)<\/jats:italic>\n and\n Rac1<\/jats:italic>\n (\n P\u2009<\u20090.01<\/jats:italic>\n ) were further affected by sh-treatment.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n Sepsis induced upregulation of integrin-receptor-complex-related genes but attenuating the upregulation of\n Ilk1<\/jats:italic>\n or\n Fermt2<\/jats:italic>\n did not affect the development of muscle weakness, although muscle fiber size was better preserved, arguing against a key role for\n Ilk1<\/jats:italic>\n or\n Fermt2<\/jats:italic>\n .\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1371\/journal.pone.0338338","type":"journal-article","created":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T18:22:38Z","timestamp":1765563758000},"page":"e0338338","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Impact of rAAV-shRNA treatment targeting 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Vanhorebeek","year":"2020","journal-title":"Intensive Care Med"},{"issue":"1","key":"pone.0338338.ref002","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1186\/s13054-015-0993-7","article-title":"Clinical review: intensive care unit acquired weakness","volume":"19","author":"G Hermans","year":"2015","journal-title":"Crit Care"},{"issue":"1","key":"pone.0338338.ref003","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1038\/ncpendmet0071","article-title":"Endocrine aspects of acute and prolonged critical illness","volume":"2","author":"I Vanhorebeek","year":"2006","journal-title":"Nat Clin Pract Endocrinol Metab"},{"issue":"3","key":"pone.0338338.ref004","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1152\/physrev.00028.2014","article-title":"The sick and the weak: Neuropathies\/Myopathies in the critically Ill","volume":"95","author":"O Friedrich","year":"2015","journal-title":"Physiol 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Vanmunster","year":"2023","journal-title":"J Appl Physiol (1985)"},{"issue":"4","key":"pone.0338338.ref036","doi-asserted-by":"crossref","first-page":"1134","DOI":"10.1152\/japplphysiol.00081.2011","article-title":"The \u03b1\u2087\u03b2\u2081-integrin increases muscle hypertrophy following multiple bouts of eccentric exercise","volume":"111","author":"K Zou","year":"2011","journal-title":"J Appl Physiol (1985)"},{"issue":"5","key":"pone.0338338.ref037","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1016\/j.ceb.2009.05.008","article-title":"How ILK and kindlins cooperate to orchestrate integrin signaling","volume":"21","author":"RT B\u00f6ttcher","year":"2009","journal-title":"Curr Opin Cell Biol"},{"issue":"5","key":"pone.0338338.ref038","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1083\/jcb.200707175","article-title":"Integrin-linked kinase stabilizes myotendinous junctions and protects muscle from stress-induced damage","volume":"180","author":"H-V Wang","year":"2008","journal-title":"J Cell Biol"},{"issue":"1","key":"pone.0338338.ref039","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1002\/jcsm.12011","article-title":"The delayed recovery of the remobilized rat tibialis anterior muscle reflects a defect in proliferative and terminal differentiation that impairs early regenerative processes","volume":"6","author":"L Slimani","year":"2015","journal-title":"J Cachexia Sarcopenia Muscle"},{"issue":"1","key":"pone.0338338.ref040","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1083\/jcb.201501006","article-title":"Kindlin-2 directly binds actin and regulates integrin outside-in signaling","volume":"213","author":"K Bledzka","year":"2016","journal-title":"J Cell Biol"},{"issue":"16","key":"pone.0338338.ref041","doi-asserted-by":"crossref","first-page":"3142","DOI":"10.1016\/j.yexcr.2006.06.030","article-title":"The Kindlins: subcellular localization and expression during murine development","volume":"312","author":"S Ussar","year":"2006","journal-title":"Exp Cell Res"},{"issue":"1","key":"pone.0338338.ref042","doi-asserted-by":"crossref","first-page":"3478","DOI":"10.1038\/s41467-024-47800-9","article-title":"CoCas9 is a compact nuclease from the human microbiome for efficient and precise genome editing","volume":"15","author":"E Pedrazzoli","year":"2024","journal-title":"Nat Commun"},{"key":"pone.0338338.ref043","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1007\/978-1-4939-9065-8_2","article-title":"Design and Assembly of CRISPR\/Cas9 Lentiviral and rAAV Vectors for Targeted Genome Editing","volume":"1937","author":"IM Sandoval","year":"2019","journal-title":"Methods Mol Biol"},{"issue":"6","key":"pone.0338338.ref044","doi-asserted-by":"crossref","first-page":"1966","DOI":"10.2353\/ajpath.2007.070555","article-title":"Deletion of integrin-linked kinase from skeletal muscles of mice resembles muscular dystrophy due to alpha 7 beta 1-integrin 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