{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T17:20:34Z","timestamp":1788283234152,"version":"build-2803163510"},"reference-count":48,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"9","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["JASN"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:sec>\n                    <jats:title>Key Points<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>\n                            <jats:italic toggle=\"yes\">De novo<\/jats:italic>\n                            nephron regeneration was achieved after partial nephrectomy in axolotls.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Tenascin C induction peaked at 2\u20134 weeks postpartial nephrectomy and coincided with cell proliferation and extracellular matrix remodeling.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Tenascin C\u2013derived peptide 6, a tenascin C\u2013derived matrikine, accelerated kidney regeneration by enhancing extracellular matrix remodeling and tenascin C expression.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Kidneys possess limited regenerative capacity. While renal tubules are capable of repair after injury, nephron loss resulting from renal mass ablation or disease is irreversible in mammals. In this study, we demonstrated\n                      <jats:italic toggle=\"yes\">de novo<\/jats:italic>\n                      nephron regeneration after partial nephrectomy in axolotls, a model organism renowned for its remarkable regenerative ability.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Kidney mass ablation was performed by using unilateral one-quarter partial nephrectomy in axolotls, and the regeneration process was assessed at multiple time points (0, 1, 2, 4, 8, 12, and 16 weeks) postsurgery.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We found that cells migrated into the wound sites and proliferated, beginning at 1 week postnephrectomy and nearly restoring the cell mass of the contralateral kidney by 4 weeks. Cell proliferation peaked between weeks 2 and 4 at the resected site and was accompanied by fibroblast activation, SOX9 expression, and induction of tenascin C. By 16 weeks after nephrectomy, new glomeruli had formed and renal tubules were\n                      <jats:italic toggle=\"yes\">de novo<\/jats:italic>\n                      regenerated and functionally matured. Notably, tenascin C expression was transiently induced, peaking at 2\u20134 weeks postsurgery and rapidly declined as cell repopulation progressed. Knockdown of tenascin C expression reduced cell proliferation and impaired regenerative process. Conversely, administration of tenascin C\u2013derived peptide 6 shifted tenascin C expression to an earlier stage and accelerated both new nephron formation and functional maturation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      These studies demonstrate\n                      <jats:italic toggle=\"yes\">de novo<\/jats:italic>\n                      nephron regeneration after partial nephrectomy in an animal model and identify tenascin C\u2013derived peptide 6 as an accelerator of kidney regeneration\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  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