title: Baicalein increases keratin 1 and 10 expression in HaCaT keratinocytes via TRPV4 receptor activation.
abstract: In this study, we characterized the effect of baicalein on the regulation of keratinocyte differentiation and proliferation, which are abnormal in atopic dermatitis or psoriasis. Treatment of HaCaT keratinocytes with 10 μm baicalein slightly inhibited cell growth, caused morphological differentiation and increased expression of keratins 1 and 10 (K1/K10) without affecting ROS generation, cytochrome c release or apoptosis. Baicalein treatment caused growth arrest in G0 /G1 phase and also induced Ca(2+) influx via TRPV4 receptor activation. Phosphorylation of ERK, Akt and p38 MAPK, but not JNK, was increased by baicalein, and inhibition of phosphorylation of ERK, but not that of Akt or p38 MAPK, blocked the baicalein-induced increase in K1/K10 expression, suggesting that ERK activation is involved in this increase. Removal of extracellular Ca(2+) or blockade of Ca(2+) influx by pharmacological inhibition or silencing of the TRPV4 receptor did not affect growth arrest, ROS generation or apoptosis, but inhibited baicalein-induced ERK phosphorylation and K1/K10 expression. Thus, baicalein treatment increases differentiation, and decreases proliferation, of keratinocytes. The mechanism of differentiation of keratinocytes is distinct from that of proliferation, the former being Ca(2+) dependent and the latter Ca(2+) independent.
authors.affiliation: Division of Plastic Surgery, Department of Surgery, Chi Mei Medical Center, Tainan, Taiwan.
authors.forename: Kuo-Feng
authors.initials: KF
authors.lastname: Huang
authors.affiliation: Department of Biology and Anatomy, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Kuo-Hsing
authors.initials: KH
authors.lastname: Ma
authors.affiliation: Department of Microbiology, Soochow University, Taipei, Taiwan.
authors.forename: Pei-Shan
authors.initials: PS
authors.lastname: Liu
authors.affiliation: Department of Biochemistry, National Defense Medical Center, Taipei, Taiwan, Republic of China.
authors.forename: Bo-Wei
authors.initials: BW
authors.lastname: Chen
authors.affiliation: Department of Biochemistry, National Defense Medical Center, Taipei, Taiwan, Republic of China.
authors.forename: Sheau-Huei
authors.initials: SH
authors.lastname: Chueh
mesh_terms: D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D004353:Drug Evaluation, Preclinical; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D044950:Flavanones / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D053556:Keratin-1 / Q000378:metabolism*; D053550:Keratin-10 / Q000378:metabolism*; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008517:Phytotherapy; D010936:Plant Extracts / Q000378:metabolism; D031364:Scutellaria baicalensis; D050916:TRPV Cation Channels / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D044950:Flavanones; C491616:KRT1 protein, human; C507493:KRT10 protein, human; D053556:Keratin-1; D010936:Plant Extracts; D050916:TRPV Cation Channels; C416986:TRPV4 protein, human; D053550:Keratin-10; C006680:baicalein; D048049:Extracellular Signal-Regulated MAP Kinases; D002118:Calcium
keywords: Ca2+ influx; ERK phosphorylation; growth arrest; keratinocyte differentiation; reactive oxygen species