کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2166453 | 1091857 | 2008 | 14 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: TRPC channels determine human keratinocyte differentiation: New insight into basal cell carcinoma TRPC channels determine human keratinocyte differentiation: New insight into basal cell carcinoma](/preview/png/2166453.png)
Aberrant keratinocyte differentiation is considered to be a key mechanism in the onset of hyperproliferative dermatological diseases, including basal cell carcinoma (BCC). It is, therefore, vital to understand what drives keratinocytes to develop such pathological phenotypes.The role of calcium in keratinocyte differentiation is uncontested but the mechanisms controlling calcium-induced differentiation have yet to be completely elucidated. This study was designed to investigate the role of calcium-permeable TRPC channels in human keratinocyte differentiation and BCC, using a combination of molecular and cell biology approaches, involving electrophysiology and Ca2+-imaging, on the HaCaT cell line, primary cultures of normal human keratinocytes, and BCC cells.We demonstrated that TRPC1/TRPC4 channel expression was important for keratinocyte differentiation, as knocking out these channels (by siRNA strategy) prevented the induction of Ca2+-induced differentiation. TRPC1/TRPC4-mediated calcium entry and endoplasmic reticulum Ca2+ content increased significantly in differentiated keratinocytes. However, the failure of BCC cells to differentiate was related to a lack of TRPC channel expression and calcium entry.In summary, our data demonstrate that TRPC1 and TRPC4 channels are key elements in keratinocyte Ca2+ homeostasis and differentiation and may therefore be responsible for skin pathologies.
Journal: Cell Calcium - Volume 43, Issue 5, May 2008, Pages 492–505