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Filopodia deposit mesangial matrix in the glomerular basement membrane (GBM), including laminin 211 which activates NF\u2010\u03baB, resulting in induction of inflammatory cytokines. Herein we show that collagen \u03b11(III) is also deposited in the GBM. Collagen \u03b11(III) localized to the mesangium in wild\u2010type mice and was found in both the mesangium and the GBM in Alport mice. We show that collagen \u03b11(III) activates discoidin domain receptor family, member 1 (DDR1) receptors both <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic>. To elucidate whether collagen \u03b11(III) might cause podocyte injury, cultured murine Alport podocytes were overlaid with recombinant collagen \u03b11(III), or not, for 24\u2009h and RNA was analyzed by RNA sequencing (RNA\u2010seq). These same cells were subjected to siRNA knockdown for integrin \u03b12 or DDR1 and the RNA was analyzed by RNA\u2010seq. Results were validated <jats:italic>in vivo<\/jats:italic> using RNA\u2010seq from RNA isolated from wild\u2010type and Alport mouse glomeruli. Numerous genes associated with podocyte injury were up\u2010 or down\u2010regulated in both Alport glomeruli and cultured podocytes treated with collagen \u03b11(III), 18 of which have been associated previously with podocyte injury or glomerulonephritis. The data indicate \u03b12\u03b21 integrin\/DDR1 co\u2010receptor signaling as the dominant regulatory mechanism. This may explain earlier studies where deletion of either DDR1 or \u03b12\u03b21 integrin in Alport mice ameliorates renal pathology. \u00a9 2022 Boys Town National Research Hospital. <jats:italic>The Journal of Pathology<\/jats:italic> published by John Wiley &amp; Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.<\/jats:p>","DOI":"10.1002\/path.5969","type":"journal-article","created":{"date-parts":[[2022,5,24]],"date-time":"2022-05-24T04:30:47Z","timestamp":1653366647000},"page":"26-37","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Glomerular basement membrane deposition of collagen \u03b11(<scp>III<\/scp>) in <scp>A<\/scp>lport glomeruli by mesangial filopodia injures podocytes via aberrant signaling through <scp>DDR1<\/scp> and integrin \u03b12\u03b21"],"prefix":"10.1002","volume":"258","author":[{"given":"Jacob","family":"Madison","sequence":"first","affiliation":[{"name":"Boys 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