{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T12:01:53Z","timestamp":1789128113632,"version":"build-2803163510"},"reference-count":66,"publisher":"American Physiological Society","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Renal Physiology"],"published-print":{"date-parts":[[2011,4]]},"abstract":"<jats:p>Podocytes are considered terminally differentiated cells in the mature kidney under normal conditions. In the face of injury, podocytes may proceed along several possible pathways, including dedifferentiation and proliferation, persistent cell cycle arrest, hypertrophy, apoptosis, or necrosis. There is mounting evidence that transdifferentiation into a dysregulated phenotype may also be a potential cell fate. We have previously reported that the transcript of SM22\u03b1, an actin-binding protein considered one of the earliest markers of smooth muscle differentiation, is upregulated nearly 70-fold in glomeruli of rats with passive Heymann nephritis (PHN). In contrast, the SM22\u03b1 transcript is absent in normal adult rat glomeruli. The purpose of this study was to define SM22\u03b1's expression during kidney development and its role in glomerular diseases characterized by podocyte injury and proteinuria. During glomerulogenesis and podocyte differentiation, SM22\u03b1 was expressed in glomeruli. This expression disappeared with glomerular maturation. Along with SM22\u03b1 induction in PHN, confirmed at both mRNA and protein levels, SM22\u03b1 was also induced across a broad range of proteinuric diseases, including experimental animal models (puromycin aminonucleoside nephropathy, adriamycin nephropathy, passive nephrotoxic nephritis, and diet-induced obesity) and human diseases (collapsing glomerulopathy, diabetic nephropathy, classic focal segmental glomerulosclerosis, IgA nephropathy, minimal-change disease, membranous nephropathy, and membranoproliferative glomerulonephritis). Crescentic glomerulonephritis was induced in SM22\u03b1 +\/+ and SM22\u03b1 \u2212\/\u2212 mice by intraperitoneal injection of sheep anti-rabbit glomeruli antibody 12.5 mg\/20 g body wt \u00d7 2 doses ( n = 12\u201315\/group), with mice euthanized at 7 and 14 days. Compared with SM22\u03b1 \u2212\/\u2212 mice, SM22\u03b1 +\/+ mice demonstrated worse disease by histopathological parameters. In addition, there was greater apoptosis (cleaved caspase-3 immunostaining), fewer podocytes (Wilms' tumor-1 immunostaining), and less proliferation (Ki-67 immunostaining) in diseased SM22\u03b1 +\/+ mice. Furthermore, there was decreased activation of Erk1\/2 in diseased SM22\u03b1 +\/+ mice. We conclude that the de novo expression of SM22\u03b1 in glomerular epithelial cells affects the course of crescentic glomerulonephritis.<\/jats:p>","DOI":"10.1152\/ajprenal.00187.2010","type":"journal-article","created":{"date-parts":[[2011,2,3]],"date-time":"2011-02-03T04:49:24Z","timestamp":1296708564000},"page":"F1026-F1042","source":"Crossref","is-referenced-by-count":31,"title":["Role of smooth muscle protein SM22\u03b1 in glomerular epithelial cell injury"],"prefix":"10.1152","volume":"300","author":[{"given":"Caroline B.","family":"Marshall","sequence":"first","affiliation":[{"name":"Divisions of 1Nephrology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ron D.","family":"Krofft","sequence":"additional","affiliation":[{"name":"Divisions of 1Nephrology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary J.","family":"Blonski","sequence":"additional","affiliation":[{"name":"Divisions of 1Nephrology 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