Glomerular parietal epithelial cells of adult murine kidney undergo EMT to generate cells with traits of renal progenitors

Tissue Engineering and Banking Laboratory, National Centre for Cell Science, Pune, India.
Journal of Cellular and Molecular Medicine (Impact Factor: 4.01). 10/2009; 15(2):396-413. DOI: 10.1111/j.1582-4934.2009.00937.x
Source: PubMed


Glomerular parietal epithelial cells (GPECs) are known to revert to embryonic phenotype in response to renal injury. However, the mechanism of de-differentiation in GPECs and the underlying cellular processes are not fully understood. In the present study, we show that cultured GPECs of adult murine kidney undergo epithelial-mesenchymal transition (EMT) to generate cells, which express CD24, CD44 and CD29 surface antigens. Characterization by qRT-PCR and immunostaining of these clonogenic cells demonstrate that they exhibit metastable phenotype with co-expression of both epithelial (cytokeratin-18) and mesenchymal (vimentin) markers. Transcript analysis by qRT-PCR revealed high expression of metanephric mesenchymal (Pax-2, WT-1, Six-1, Eya-1, GDNF) and uteric bud (Hoxb-7, C-Ret) genes in these cells, indicating their bipotent progenitor status. Incubation of GPECs with EMT blocker Prostaglandin E2, resulted in low expression of renal progenitor markers reflecting the correlation between EMT and acquired stemness in these cells. Additional in vitro renal commitment assays confirmed their functional staminality. When injected into E13.5 kidney rudiments, the cells incorporated into the developing kidney primordia and co-culture with E13.5 spinal cord resulted in branching and tubulogenesis in these cells. When implanted under renal capsule of unilaterally nephrectomized mice, these cells differentiated into immature glomeruli and vascular ducts. Our study demonstrates that EMT plays a major role in imparting plasticity to terminally differentiated GPECs by producing metastable cells with traits of kidney progenitors. The present study would improve our understanding on epithelial cell plasticity, furthering our knowledge of its role in renal repair and regeneration.

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Available from: Vikash Chandra, Jan 02, 2015
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    • "Taking into account the present study, we suppose that PEC type II epithelial-to-mesenchymal transition, induced by TGF-β1 and ZEB 2 overexpression, could be related to the loss of their well-defined cell-cell and cell-basement membrane contacts, thus allowing their migration to glomerular vascular stalk becoming morphologically similar to podocytes. A recent study have demonstrated that EMT plays a major role in imparting plasticity to terminally differentiated PECs by producing metastable cells with traits of kidney progenitors [33]. Also, Zhang et al. (2012) found in aging nephropathy an increased number of PECs and PECs expressing podocyte proteins [34]. "
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    • "Additional lineage tracing in adults is needed to further support the model. Other studies that isolated self-renewing cell lines from human and mouse glomeruli reported that these cells express various developmental genes [95,96]. Uncovering the roles of these genes could provide useful mechanistic insights into PEC behavior. "
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    • "It still remains to be elucidated whether a full or partial EMT process would play a similar role in induction of reprogramming of cells of an epithelial origin. EMT inducers are silent during adulthood however EMT and MET can be activated during regeneration processes, including wound healing, kidney, liver and heart regeneration [15], [16], [45], [46]. Abnormal activation of EMT in adults can be detrimental [4]. "
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