Merck

MKL1 inhibits cell cycle progression through p21 in podocytes.

BMC molecular biology (2015-04-19)
Shuang Yang, Lingjia Liu, Pengjuan Xu, Zhuo Yang
ABSTRACT

The glomerular podocyte is a highly specialized cell type with the ability to ultrafilter blood and support glomerular capillary pressure. However, little is known about the genetic programs leading to this functionality or the final phenotype. In the current study, we found that the expression of a myocardin/MKL family member, MKL1, was significantly upregulated during cell cycle arrest induced by a temperature switch in murine podocyte clone 5 (MPC5) cells. Further investigation demonstrated that overexpression of MKL1 led to inhibition of cell proliferation by decreasing the number of cells in S phase of the cell cycle. In contrast, MKL1 knockdown by RNA interference had the opposite effect, highlighting a potential role of MKL1 in blocking G1/S transition of the cell cycle in MPC5 cells. Additionally, using an RT(2) Profiler PCR Array, p21 was identified as a direct target of MKL1. We further revealed that MKL1 activated p21 transcription by recruitment to the CArG element in its promoter, thus resulting in cell cycle arrest. In addition, the expression of MKL1 is positively correlated with that of p21 in podocytes in postnatal mouse kidney and significantly upregulated during the morphological switch of podocytes from proliferation to differentiation. Our observations demonstrate that MKL1 has physiological roles in the maturation and development of podocytes, and thus its misregulation might lead to glomerular and renal dysfunction.

MATERIALS
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