Wnt/β-Catenin and Wnt5a/Ca2+ Pathways Regulate Proliferation and Apoptosis of Keratinocytes in Psoriasis Lesions

Abstract

Background/Aims: Wnt5a is overexpressed in psoriasis lesions, however the mechanism by which Wnt5a is involved in the pathogenesis of psoriasis is not clear. To address this, the expression of Wnt5a in psoriatic lesions and its effect on keratinocyte cell proliferation and apoptosis was examined in vitro. Methods: The expression levels of WNT5A, and genes encoding its receptors frizzled2 (FZD2) and frizzled5 (FZD5) were examined in samples obtained from individuals with psoriasis and healthy controls. Knockdown of Wnt5a with short interfering (si)RNAs was performed in cultured HaCaT keratinocytes and normal human keratinocytes (NHK), and the expression of Wnt5a, protein kinase C (PKC), and β-catenin were determined, and cell cycle activity, proliferation and apoptosis were assessed. Results: The expression of WNT5A, FZD2 and FZD5 mRNA and protein were increased in psoriatic lesions. Wnt5a knockdown suppressed proliferation and induced apoptosis in HaCaT and NHK cells. Additionally, expression of PCNA, MKI67, CCND1, BCL2, CTNNB1, and genes encoding PKC and survivin were downregulated, whereas CASP3 was upregulated. The mRNA levels of the Wnt pathway inhibitors DKK1 and SFRP1 were upregulated, Western blotting analyses demonstrated reduction in β-catenin and PKC protein levels. Conclusion: Knockdown of Wnt5a suppresses the proliferation of keratinocytes and induces apoptosis by inhibiting the Wnt/β-catenin or Wnt5a/Ca²⁺ pathways.

Benzo(a)pyrene inhibits endometrial cell apoptosis in early pregnant mice via the WNT5A pathway

“…During the implantation window, appropriate apoptosis of the uterine epithelium and stromal cells facilitates embryo attachment to the endometrial epithelium and the subsequent invasion into the endometrial stroma (Boeddeker & Hess, ). Zhang et al () found that knocking down WNT5A induces apoptosis by inhibiting WNT/β‐catenin. Griesmann et al () also proved that knocking down WNT5A significantly increases drug‐induced apoptosis.…”

Terminalia Chebulanin Attenuates Psoriatic Skin Lesion via Regulation of Heme Oxygenase-1

“…Psoriasis is a result of the interaction of genetic predisposition and external stimuli including stress, infection, trauma, and drugs [2][3][4]. This disease is characterized by a series of linked cellular changes in the skin, including hyperproliferative keratinocytes, parakeratosis, hyperkeratosis, and infiltration of inflammatory leukocytes into the dermis and epidermis, resulting in a thickened epidermis [5,6]. The mechanism of psoriasis is still not completely understood.…”

A unified mitochondria mechanistic target of rapamycin acyl‐coenzyme A dehydrogenase 10 signal relay modulation for metformin growth inhibition in human immortalized keratinocytes cells

“…The body adjusts keratinocyte proliferation and regulates the growth and differentiation of epidermal cells through apoptosis. Apoptosis offsets keratinocyte proliferation and regulates the formation of stratum corneum, and improper functioning of apoptotic pathways leads to the development of several skin diseases . Psoriatic keratinocytes exhibit an enhanced ability to resist apoptosis, which may be one of the key factors in the pathogenesis of psoriasis, while metformin is known as an antiproliferation drug in major cell lines and tissues.…”

“…Psoriasis is a common chronic inflammatory disease which is characterized by abnormal proliferation and differentiation of keratinocytes . Although the exact mechanism of psoriasis is not yet clearly understood, the enhanced proliferation of keratinocytes and inflammation are considered to be the key events that contribute to its development . Therefore, inhibition of excessive proliferation of keratinocytes may lead to the prevention and treatment of psoriasis.…”