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Apoptosis in podocytes induced by TGF-β and Smad7
Open accessAbstract
Primary and secondary forms of focal segmental glomerulosclerosis (FSGS) are characterized by depletion of podocytes and constitute a central manifestation of chronic progressive glomerular diseases. Here we report that podocytes undergo apoptosis at early stages in the course of progressive glomerulosclerosis in TGF-beta1 transgenic mice. Apoptosis is associated with progressive depletion of podocytes and precedes mesangial expansion. Smad7 protein expression is strongly induced specifically in damaged podocytes of transgenic mice and in cultured murine podocytes treated with TGF-beta. TGF-beta1 and Smad7 each induce apoptosis in podocytes, and their coexpression has an additive effect. Activation of p38 MAP kinase and caspase-3 is required for TGF-beta-mediated apoptosis, but not for apoptosis induced by Smad7. Unlike TGF-beta, Smad7 inhibits nuclear translocation and transcriptional activity of the cell survival factor NF-kappaB. Our results suggest a novel functional role for Smad7 as amplifier of TGF-beta-induced apoptosis in podocytes and a new pathomechanism for podocyte depletion in progressive glomerulosclerosis.
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Cites
Arteaga, C. L., Hurd, S. D., Winnier, A. R., Johnson, M. D., Fendly, B. M., & Forbes, J. T. (1993) · Journal of Clinical Investigation · doi:10.1172/jci116871 · Cited by 359
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Meng, X.-M., Nikolic-Paterson, D. J., & Lan, H. Y. (2016) · Nature Reviews Nephrology · doi:10.1038/nrneph.2016.48 · Cited by 3,528
Cell biology of the glomerular podocyte
Pavenstädt, H., Kriz, W., & Kretzler, M. (2003) · Physiological Reviews · doi:10.1152/physrev.00020.2002 · Cited by 1,499
The podocyte’s response to injury: role in proteinuria and glomerulosclerosis
Shankland, S. J. (2006) · Kidney International · doi:10.1038/sj.ki.5000410 · Cited by 846
Diabetes and Kidney Disease: Role of Oxidative Stress
Jha, J. C., Banal, C., Chow, B. S. M., Cooper, M. E., & Jandeleit-Dahm, K. (2016) · Antioxidants & Redox Signaling · doi:10.1089/ars.2016.6664 · Cited by 660
Regulation of TGF-β Family Signaling by Inhibitory Smads
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Metadata
- Authors
- Schiffer, M., Bitzer, M., Roberts, I. S. D., Kopp, J. B., ten Dijke, P., Mundel, P., & Böttinger, E. P.
- Venue
- Journal of Clinical Investigation
- Published
- 2001-09-15
- Volume
- 108
- Issue
- 6
- Pages
- 807-816
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W2097887036
- Cited by
- 598
- References
- 1
- FWCI
- 14.75
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Schiffer, M., Bitzer, M., Roberts, I. S. D., Kopp, J. B., ten Dijke, P., Mundel, P., & Böttinger, E. P. (2001). Apoptosis in podocytes induced by TGF-β and Smad7. Journal of Clinical Investigation. https://doi.org/10.1172/jci12367
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
