{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T15:50:34Z","timestamp":1787500234324,"version":"build-2736575974"},"reference-count":162,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,4,12]],"date-time":"2021-04-12T00:00:00Z","timestamp":1618185600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Physiol."],"abstract":"<jats:p>\n                    New insights into the cellular and extra-cellular composition of scar tissue after myocardial infarction (MI) have been identified. Recently, a heterogeneous podoplanin-expressing cell population has been associated with fibrogenic and inflammatory responses and lymphatic vessel growth during scar formation. Podoplanin is a mucin-like transmembrane glycoprotein that plays an important role in heart development, cell motility, tumorigenesis, and metastasis. In the adult mouse heart, podoplanin is expressed only by cardiac lymphatic endothelial cells; after MI, it is acquired with an unexpected heterogeneity by PDGFR\u03b1-, PDGFR\u03b2-, and CD34-positive cells. Podoplanin may therefore represent a sign of activation of a cohort of progenitor cells during different phases of post-ischemic myocardial wound repair. Podoplanin binds to C-type lectin-like receptor 2 (CLEC-2) which is exclusively expressed by platelets and a variety of immune cells. CLEC-2 is upregulated in CD11b\n                    <jats:sup>high<\/jats:sup>\n                    cells, including monocytes and macrophages, following inflammatory stimuli. We recently published that inhibition of the interaction between podoplanin-expressing cells and podoplanin-binding cells using podoplanin-neutralizing antibodies reduces but does not fully suppress inflammation post-MI while improving heart function and scar composition after ischemic injury. These data support an emerging and alternative mechanism of interactome in the heart that, when neutralized, leads to altered inflammatory response and preservation of cardiac function and structure. The overarching objective of this review is to assimilate and discuss the available evidence on the functional role of podoplanin-positive cells on cardiac fibrosis and remodeling. A detailed characterization of cell-to-cell interactions and paracrine signals between podoplanin-expressing cells and the other type of cells that compose the heart tissue is needed to open a new line of investigation extending beyond the known function of these cells. This review attempts to discuss the role and biology of podoplanin-positive cells in the context of cardiac injury, repair, and remodeling.\n                  <\/jats:p>","DOI":"10.3389\/fphys.2021.667278","type":"journal-article","created":{"date-parts":[[2021,4,12]],"date-time":"2021-04-12T03:16:58Z","timestamp":1618197418000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":16,"title":["Role of Podoplanin-Positive Cells in Cardiac Fibrosis and Angiogenesis After Ischemia"],"prefix":"10.3389","volume":"12","author":[{"given":"Maria","family":"Cimini","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raj","family":"Kishore","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,4,12]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"276","DOI":"10.1016\/j.immuni.2012.05.022","article-title":"Podoplanin-rich stromal networks induce dendritic cell motility via activation of the C-type lectin receptor CLEC-2.","volume":"37","author":"Acton","year":"2012","journal-title":"Immunity"},{"key":"B2","doi-asserted-by":"publisher","first-page":"498","DOI":"10.1038\/nature13814","article-title":"Dendritic cells control fibroblastic reticular network tension and lymph node expansion.","volume":"514","author":"Acton","year":"2014","journal-title":"Nature"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1783","DOI":"10.1111\/jcmm.12624","article-title":"The secretome of myocardial telocytes modulates the activity of cardiac stem cells.","volume":"19","author":"Albulescu","year":"2015","journal-title":"J. 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