{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T20:43:39Z","timestamp":1789418619017,"version":"build-2803163510"},"reference-count":46,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JASN"],"published-print":{"date-parts":[[2018,5]]},"abstract":"<jats:p>\n                    <jats:bold>Background<\/jats:bold>\n                    FSGS is a pattern of podocyte injury that leads to loss of glomerular function. Podocytes support other podocytes and glomerular capillary structure, oppose hemodynamic forces, form the slit diaphragm, and have mechanical properties that permit these functions. However, the biophysical characteristics of glomeruli and podocytes in disease remain unclear.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Methods<\/jats:bold>\n                    Using microindentation, atomic force microscopy, immunofluorescence microscopy, quantitative RT-PCR, and a three-dimensional collagen gel contraction assay, we studied the biophysical and structural properties of glomeruli and podocytes in chronic (Tg26 mice [HIV protein expression]) and acute (protamine administration [cytoskeletal rearrangement]) models of podocyte injury.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Results<\/jats:bold>\n                    Compared with wild-type glomeruli, Tg26 glomeruli became progressively more deformable with disease progression, despite increased collagen content. Tg26 podocytes had disordered cytoskeletons, markedly abnormal focal adhesions, and weaker adhesion; they failed to respond to mechanical signals and exerted minimal traction force in three-dimensional collagen gels. Protamine treatment had similar but milder effects on glomeruli and podocytes.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Conclusions<\/jats:bold>\n                    Reduced structural integrity of Tg26 podocytes causes increased deformability of glomerular capillaries and limits the ability of capillaries to counter hemodynamic force, possibly leading to further podocyte injury. Loss of normal podocyte mechanical integrity could injure neighboring podocytes due to the absence of normal biophysical signals required for podocyte maintenance. The severe defects in podocyte mechanical behavior in the Tg26 model may explain why Tg26 glomeruli soften progressively, despite increased collagen deposition, and may be the basis for the rapid course of glomerular diseases associated with severe podocyte injury. In milder injury (protamine), similar processes occur but over a longer time.\n                  <\/jats:p>","DOI":"10.1681\/asn.2017050475","type":"journal-article","created":{"date-parts":[[2018,3,23]],"date-time":"2018-03-23T09:06:36Z","timestamp":1521795996000},"page":"1501-1512","source":"Crossref","is-referenced-by-count":31,"title":["Similar Biophysical Abnormalities in Glomeruli and Podocytes from Two Distinct Models"],"prefix":"10.1681","volume":"29","author":[{"given":"Addie E.","family":"Embry","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Division of Nephrology, University of Texas Southwestern Medical Center, Dallas, Texas;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Nephrology, University of Texas Southwestern Medical Center, Dallas, Texas;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel M.","family":"Henderson","sequence":"additional","affiliation":[{"name":"Department of Pathology, Boston University School of Medicine, Boston, Massachusetts;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F. Jefferson","family":"Byfield","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, Pennsylvania;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liping","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Nephrology, University of Texas Southwestern Medical Center, Dallas, Texas;"},{"name":"Department of Medicine, Dallas Veterans Affairs Medical Center, Dallas, Texas;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joonho","family":"Yoon","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Nephrology, University of Texas Southwestern Medical Center, Dallas, Texas;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenzhen","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Medicine, Cleveland Clinic Foundation, Cleveland, Ohio;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrina","family":"Cruz","sequence":"additional","affiliation":[{"name":"Department of Pathology, Boston University School of Medicine, Boston, Massachusetts;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Moradi","sequence":"additional","affiliation":[{"name":"Department of Pathology, Boston University School of Medicine, Boston, Massachusetts;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. Barton","family":"Gillombardo","sequence":"additional","affiliation":[{"name":"Department of Medicine, Cleveland Clinic Foundation, Cleveland, Ohio;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rihanna Z.","family":"Hussain","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Texas Southwestern Medical School, Dallas, Texas; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Doelger","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Texas Southwestern Medical School, Dallas, Texas; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olaf","family":"Stuve","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Texas Southwestern Medical School, Dallas, Texas; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Audrey N.","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Nephrology, University of Texas Southwestern Medical Center, Dallas, Texas;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul A.","family":"Janmey","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, Pennsylvania;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leslie A.","family":"Bruggeman","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. Tyler","family":"Miller","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Nephrology, University of Texas Southwestern Medical Center, Dallas, Texas;"},{"name":"Department of Medicine, Dallas Veterans Affairs Medical Center, Dallas, Texas;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2018,3,23]]},"reference":[{"key":"B1-20231016","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1038\/nrneph.2014.216","article-title":"Causes and pathogenesis of focal segmental glomerulosclerosis.","volume":"11","author":"Fogo","year":"2015","journal-title":"Nat Rev Nephrol"},{"key":"B2-20231016","doi-asserted-by":"crossref","first-page":"1275","DOI":"10.1681\/ASN.2010090963","article-title":"Podocyte injury damages other podocytes.","volume":"22","author":"Matsusaka","year":"2011","journal-title":"J Am Soc Nephrol"},{"key":"B3-20231016","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1007\/s00424-017-2012-0","article-title":"Mechanical challenges to the glomerulus and podocyte loss: Evolution of a paradigm.","volume":"469","author":"Lemley","year":"2017","journal-title":"Pflugers Arch"},{"key":"B4-20231016","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1681\/ASN.2014030278","article-title":"A potential role for mechanical forces in the detachment of podocytes and the progression of CKD.","volume":"26","author":"Kriz","year":"2015","journal-title":"J Am Soc Nephrol"},{"key":"B5-20231016","doi-asserted-by":"crossref","first-page":"e0167924","DOI":"10.1371\/journal.pone.0167924","article-title":"Biochemical and cellular determinants of renal glomerular elasticity.","volume":"11","author":"Embry","year":"2016","journal-title":"PLoS One"},{"key":"B6-20231016","doi-asserted-by":"crossref","first-page":"43934","DOI":"10.1038\/srep43934","article-title":"A biomimetic gelatin-based platform elicits a pro-differentiation effect on podocytes through mechanotransduction.","volume":"7","author":"Hu","year":"2017","journal-title":"Sci Rep"},{"key":"B7-20231016","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1016\/j.cell.2006.06.044","article-title":"Matrix elasticity directs stem cell lineage specification.","volume":"126","author":"Engler","year":"2006","journal-title":"Cell"},{"key":"B8-20231016","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/j.semnephrol.2012.06.004","article-title":"The challenge and response of podocytes to glomerular hypertension.","volume":"32","author":"Endlich","year":"2012","journal-title":"Semin Nephrol"},{"key":"B9-20231016","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1038\/ki.1994.47","article-title":"A role for podocytes to counteract capillary wall distension.","volume":"45","author":"Kriz","year":"1994","journal-title":"Kidney Int"},{"key":"B10-20231016","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1073\/pnas.89.5.1577","article-title":"Progressive glomerulosclerosis and enhanced renal accumulation of basement membrane components in mice transgenic for human immunodeficiency virus type 1 genes.","volume":"89","author":"Kopp","year":"1992","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B11-20231016","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1172\/JCI119525","article-title":"Nephropathy in human immunodeficiency virus-1 transgenic mice is due to renal transgene expression.","volume":"100","author":"Bruggeman","year":"1997","journal-title":"J Clin Invest"},{"key":"B12-20231016","doi-asserted-by":"crossref","first-page":"1700","DOI":"10.1046\/j.1523-1755.1999.00729.x","article-title":"Polycations induce calcium signaling in glomerular podocytes.","volume":"56","author":"R\u00fcdiger","year":"1999","journal-title":"Kidney Int"},{"key":"B13-20231016","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1681\/ASN.2016040414","article-title":"Synaptopodin is a coincidence detector of tyrosine versus serine\/threonine phosphorylation for the modulation of rho protein crosstalk in podocytes.","volume":"28","author":"Buvall","year":"2017","journal-title":"J Am Soc Nephrol"},{"key":"B14-20231016","doi-asserted-by":"crossref","first-page":"F701","DOI":"10.1152\/ajprenal.00246.2006","article-title":"HIV infection changes glomerular podocyte cytoskeletal composition and results in distinct cellular mechanical properties.","volume":"292","author":"Tandon","year":"2007","journal-title":"Am J Physiol Renal Physiol"},{"key":"B15-20231016","doi-asserted-by":"crossref","first-page":"2079","DOI":"10.1681\/ASN.V11112079","article-title":"Renal epithelium is a previously unrecognized site of HIV-1 infection.","volume":"11","author":"Bruggeman","year":"2000","journal-title":"J Am Soc Nephrol"},{"key":"B16-20231016","doi-asserted-by":"crossref","first-page":"8173","DOI":"10.1074\/jbc.M708920200","article-title":"HIV-1 Nef disrupts the podocyte actin cytoskeleton by interacting with diaphanous interacting protein.","volume":"283","author":"Lu","year":"2008","journal-title":"J Biol Chem"},{"key":"B17-20231016","doi-asserted-by":"crossref","first-page":"1048","DOI":"10.1111\/j.1523-1755.2005.00497.x","article-title":"Expression of HIV-1 genes in podocytes alone can lead to the full spectrum of HIV-1-associated nephropathy.","volume":"68","author":"Zhong","year":"2005","journal-title":"Kidney Int"},{"key":"B18-20231016","doi-asserted-by":"crossref","first-page":"201","DOI":"10.5858\/133.2.201","article-title":"Advances in the biology and genetics of the podocytopathies: Implications for diagnosis and therapy.","volume":"133","author":"Barisoni","year":"2009","journal-title":"Arch Pathol Lab Med"},{"key":"B19-20231016","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1038\/nrneph.2009.139","article-title":"Controversies in the pathogenesis of HIV-associated renal diseases.","volume":"5","author":"Bruggeman","year":"2009","journal-title":"Nat Rev Nephrol"},{"key":"B20-20231016","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1038\/nrneph.2015.9","article-title":"HIV-associated nephropathies: Epidemiology, pathology, mechanisms and treatment.","volume":"11","author":"Rosenberg","year":"2015","journal-title":"Nat Rev Nephrol"},{"key":"B21-20231016","first-page":"805","article-title":"The altered glomerular filtration slits seen in puromycin aminonucleoside nephrosis and protamine sulfate-treated rats contain the tight junction protein ZO-1.","volume":"141","author":"Kurihara","year":"1992","journal-title":"Am J Pathol"},{"key":"B22-20231016","doi-asserted-by":"crossref","first-page":"F213","DOI":"10.1152\/ajprenal.90421.2008","article-title":"Inducible rodent models of acquired podocyte diseases.","volume":"296","author":"Pippin","year":"2009","journal-title":"Am J Physiol Renal Physiol"},{"key":"B23-20231016","doi-asserted-by":"crossref","first-page":"1453","DOI":"10.1681\/ASN.2010080878","article-title":"Calcium mediates glomerular filtration through calcineurin and mTORC2\/Akt signaling.","volume":"22","author":"Vassiliadis","year":"2011","journal-title":"J Am Soc Nephrol"},{"key":"B24-20231016","doi-asserted-by":"crossref","first-page":"1677","DOI":"10.1681\/ASN.V1281677","article-title":"Human immunodeficiency virus-1 induces loss of contact inhibition in podocytes.","volume":"12","author":"Schwartz","year":"2001","journal-title":"J Am Soc Nephrol"},{"key":"B25-20231016","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1006\/excr.1997.3739","article-title":"Rearrangements of the cytoskeleton and cell contacts induce process formation during differentiation of conditionally immortalized mouse podocyte cell lines.","volume":"236","author":"Mundel","year":"1997","journal-title":"Exp Cell Res"},{"key":"B26-20231016","doi-asserted-by":"crossref","first-page":"194120","DOI":"10.1088\/0953-8984\/22\/19\/194120","article-title":"A simple indentation device for measuring micrometer-scale tissue stiffness.","volume":"22","author":"Levental","year":"2010","journal-title":"J Phys Condens Matter"},{"key":"B27-20231016","doi-asserted-by":"crossref","first-page":"5095","DOI":"10.1016\/j.bpj.2009.03.046","article-title":"Absence of filamin A prevents cells from responding to stiffness gradients on gels coated with collagen but not fibronectin.","volume":"96","author":"Byfield","year":"2009","journal-title":"Biophys J"},{"key":"B28-20231016","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/j.yexcr.2014.04.013","article-title":"The different roles of myosin IIA and myosin IIB in contraction of 3D collagen matrices by human fibroblasts.","volume":"326","author":"Liu","year":"2014","journal-title":"Exp Cell Res"},{"key":"B29-20231016","doi-asserted-by":"crossref","first-page":"C397","DOI":"10.1152\/ajpcell.00438.2010","article-title":"Biophysical properties of normal and diseased renal glomeruli.","volume":"300","author":"Wyss","year":"2011","journal-title":"Am J Physiol Cell Physiol"},{"key":"B30-20231016","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1046\/j.1523-1755.2000.00152.x","article-title":"HIV-1 induces renal epithelial dedifferentiation in a transgenic model of HIV-associated nephropathy.","volume":"58","author":"Barisoni","year":"2000","journal-title":"Kidney Int"},{"key":"B31-20231016","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1681\/ASN.V10151","article-title":"The dysregulated podocyte phenotype: A novel concept in the pathogenesis of collapsing idiopathic focal segmental glomerulosclerosis and HIV-associated nephropathy.","volume":"10","author":"Barisoni","year":"1999","journal-title":"J Am Soc Nephrol"},{"key":"B32-20231016","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1097\/QAD.0b013e328351f6cf","article-title":"Glomerular MYH9 expression is reduced by HIV-1.","volume":"26","author":"Hays","year":"2012","journal-title":"AIDS"},{"key":"B33-20231016","doi-asserted-by":"crossref","first-page":"21137","DOI":"10.1074\/jbc.M117.819029","article-title":"The Hippo pathway regulator KIBRA promotes podocyte injury by inhibiting YAP signaling and disrupting actin cytoskeletal dynamics.","volume":"292","author":"Meliambro","year":"2017","journal-title":"J Biol Chem"},{"key":"B35-20231016","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1681\/ASN.2014090916","article-title":"Podocyte-specific deletion of yes-associated protein causes FSGS and progressive renal failure.","volume":"27","author":"Schwartzman","year":"2016","journal-title":"J Am Soc Nephrol"},{"key":"B36-20231016","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1186\/s12882-016-0287-6","article-title":"RhoA deficiency disrupts podocyte cytoskeleton and induces podocyte apoptosis by inhibiting YAP\/dendrin signal.","volume":"17","author":"Huang","year":"2016","journal-title":"BMC Nephrol"},{"key":"B37-20231016","doi-asserted-by":"crossref","first-page":"3117","DOI":"10.1681\/ASN.2015050499","article-title":"YAP\/TAZ are mechanoregulators of TGF-\u00b7-Smad signaling and renal fibrogenesis.","volume":"27","author":"Szeto","year":"2016","journal-title":"J Am Soc Nephrol"},{"key":"B38-20231016","doi-asserted-by":"crossref","first-page":"2976","DOI":"10.1038\/ncomms3976","article-title":"Inactivation of the Hippo tumour suppressor pathway by integrin-linked kinase.","volume":"4","author":"Serrano","year":"2013","journal-title":"Nat Commun"},{"key":"B39-20231016","doi-asserted-by":"crossref","first-page":"1731","DOI":"10.1681\/ASN.V5101731","article-title":"Structure-stabilizing forces in the glomerular tuft.","volume":"5","author":"Kriz","year":"1995","journal-title":"J Am Soc Nephrol"},{"key":"B40-20231016","doi-asserted-by":"crossref","first-page":"e0146588","DOI":"10.1371\/journal.pone.0146588","article-title":"Normal and fibrotic rat livers demonstrate shear strain softening and compression stiffening: A model for soft tissue mechanics.","volume":"11","author":"Perepelyuk","year":"2016","journal-title":"PLoS One"},{"key":"B41-20231016","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1007\/BF00366667","article-title":"Strain hardening of fibrin gels and plasma clots.","volume":"36","author":"Shah","year":"1997","journal-title":"Rheol Acta"},{"key":"B42-20231016","doi-asserted-by":"crossref","first-page":"19270","DOI":"10.1038\/srep19270","article-title":"Uncoupling shear and uniaxial elastic moduli of semiflexible biopolymer networks: Compression-softening and stretch-stiffening.","volume":"6","author":"van Oosten","year":"2016","journal-title":"Sci Rep"},{"key":"B43-20231016","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1681\/ASN.2012040414","article-title":"Adiponectin promotes functional recovery after podocyte ablation.","volume":"24","author":"Rutkowski","year":"2013","journal-title":"J Am Soc Nephrol"},{"key":"B44-20231016","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1681\/ASN.2011050486","article-title":"Podocyte injury can be catching.","volume":"22","author":"D\u2019Agati","year":"2011","journal-title":"J Am Soc Nephrol"},{"key":"B45-20231016","doi-asserted-by":"crossref","first-page":"3162","DOI":"10.1681\/ASN.2014080752","article-title":"Glomerular aging and focal global sclerosis: A podometric perspective.","volume":"26","author":"Hodgin","year":"2015","journal-title":"J Am Soc Nephrol"},{"key":"B46-20231016","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1172\/JCI119163","article-title":"Podocyte loss and progressive glomerular injury in type II diabetes.","volume":"99","author":"Pagtalunan","year":"1997","journal-title":"J Clin Invest"},{"key":"B47-20231016","doi-asserted-by":"crossref","first-page":"2953","DOI":"10.1681\/ASN.2005050488","article-title":"Podocyte hypertrophy, \u201cadaptation,\u201d and \u201cdecompensation\u201d associated with glomerular enlargement and glomerulosclerosis in the aging rat: Prevention by calorie restriction.","volume":"16","author":"Wiggins","year":"2005","journal-title":"J Am Soc Nephrol"}],"container-title":["Journal of the American Society of Nephrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/00001751-201805000-00019","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T19:30:46Z","timestamp":1786131046000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/00001751-201805000-00019"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,3,23]]},"references-count":46,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2018]]}},"URL":"https:\/\/doi.org\/10.1681\/asn.2017050475","relation":{},"ISSN":["1046-6673","1533-3450"],"issn-type":[{"value":"1046-6673","type":"print"},{"value":"1533-3450","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,3,23]]}}}