{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T09:53:51Z","timestamp":1781344431708,"version":"3.54.1"},"reference-count":45,"publisher":"American Society for Clinical Investigation","issue":"9","funder":[{"name":"national institute of health","award":["R01 DK110023"],"award-info":[{"award-number":["R01 DK110023"]}]},{"name":"national institute of health","award":["K08 HL145138"],"award-info":[{"award-number":["K08 HL145138"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,5,7]]},"abstract":"<jats:p>\n                    Therapeutic complement inhibition is a major focus for novel drug development. Of upstream targets, factor D (FD) is appealing because it circulates in plasma at low concentrations and has a single function: to cleave factor B to generate C3 convertase of the alternative pathway (AP). Mice with a targeted deletion of factor H (FH;\n                    <jats:italic>\n                      Cfh\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    mice) develop C3 glomerulopathy (C3G) due to uncontrolled AP activity. To assess the impact of FD inhibition, we studied\n                    <jats:italic>\n                      Cfh\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    <jats:italic>\n                      Cfd\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    mice. We show that C3G in\n                    <jats:italic>\n                      Cfh\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    mice is not rescued by removing FD. We used serum from\n                    <jats:italic>\n                      Cfh\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    <jats:italic>\n                      Cfd\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    mice to demonstrate that residual AP function occurs even when both FD and FH are missing and that hemolytic activity is present due to the action of C3(H\n                    <jats:sub>2<\/jats:sub>\n                    O). We propose that uncontrolled tick-over leads to slow activation of the AP in\n                    <jats:italic>\n                      Cfh\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    <jats:italic>\n                      Cfd\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    mice and that a minimal threshold of FH is necessary if tissue deposition of C3 is to be prevented. The FD\/FH ratio dictates serum C3 level and renal C3b deposition. In C3G patients with chronic renal disease, the FD\/FH ratio correlates inversely with C3 and C5 serum levels, suggesting that continuous AP control may be difficult to achieve by targeting FD.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.135758","type":"journal-article","created":{"date-parts":[[2020,5,6]],"date-time":"2020-05-06T11:01:37Z","timestamp":1588762897000},"source":"Crossref","is-referenced-by-count":23,"title":["C3(H2O) prevents rescue of complement-mediated C3 glomerulopathy in Cfh\u2013\/\u2013 Cfd\u2013\/\u2013 mice"],"prefix":"10.1172","volume":"5","author":[{"given":"Yuzhou","family":"Zhang","sequence":"first","affiliation":[{"name":"Molecular Otolaryngology and Renal Research Laboratories, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Keenan","sequence":"additional","affiliation":[{"name":"Molecular Otolaryngology and Renal Research Laboratories, 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