Dynamic alterations in m6A RNA methylation profiles during involution of infantile hemangiomas

IntroductionInfantile hemangioma (IH) is a common benign vascular tumor characterized by a proliferative phase followed by regression. N6-methyladenosine (m6A) methylation, a major RNA modification, plays a critical role in tumor development, though its function in IH remains unclear.MethodsThis study analyzed six IH samples (three from proliferative IH, three from involuting IH), using transcript-specific microarrays after m6A immunoprecipitation to explore dynamic methylation changes and their regulatory impact on gene expression.ResultsResults showed significantly lower m6A levels in involuting-phase hemangiomas. Differentially methylated genes (DMGs) were mainly involved in biological processes such as cell-cell junction and cell-matrix adhesion. KEGG pathway analysis revealed DMGs were enriched in MAPK, Calcium, and PI3K-Akt signaling pathways, suggesting that m6A modifications are closely linked to angiogenesis and tumor growth. MeRIP-qPCR showed that IGF1 and IGF2 exhibiting significant correlation in both m6A levels and expression. The overall downregulation of m6A modification for lncRNA and sncRNA suggested active demethylation processes may involve in involution of IH.DiscussionOverall, this study demonstrates that m6A methylation modulates key cellular pathways in IH progression and may serve as a promising target for future diagnostic and therapeutic strategies

CCN1, a Pro-Inflammatory Factor, Aggravates Psoriasis Skin Lesions by Promoting Keratinocyte Activation

Psoriasis is a common chronic skin disease characterized by epidermal hyperplasia and inflammation. The pathogenesis of psoriasis is multifactorial and is not fully understood. Here we demonstrate that CCN1 (also called Cyr61, which is short for cysteine-rich 61), an extracellular matrix protein that is also considered a pro-inflammatory factor, is highly expressed in the lesional skin of psoriasis patients, as well as in that of imiquimod (IMQ)- and IL-23-treated psoriasis-like mice. Then we show that blocking CCN1 function in vivo attenuates epidermal hyperplasia and inflammation in psoriasis-like mice. Further, in primary cultured normal human keratinocytes and HaCaT (human keratinocyte cell line) cells, CCN1 promotes keratinocyte activation, including the proliferation and expression of immune-related molecules. Finally, we observe that integrin α6β1 is the receptor of CCN1 in keratinocytes, and CCN1 stimulation activates the downstream phosphoinositide-3 kinase/Akt/NF-κB signaling pathway. Taken together, our findings reveal that CCN1 has a critical role in psoriasis pathogenesis. Moreover, as CCN1 is a secreted extracellular matrix (ECM) protein, our study also provides evidence that ECM, which is involved in psoriatic pathogenesis, could be a potent target for psoriasis treatment

The profile of Cyr61 expression data correlate to the skin inflammation in psoriasis

The data presented in this article are related to the research article entitled “Cyr61/CCN1 is involved in the pathogenesis of psoriasis vulgaris via promoting IL-8 production by keratinocytes in a JNK/NF-κB pathway” (Pinru Wu, Gang Ma, Xianjin Zhu, Ting Gu, Jie Zhang, Yue Sun, Hui Xu, Rongfen Huo, Beiqing Wang, Baihua Shen, Xiangdong Chen, Ningli Li, 2016) [1]. Cysteine-rich 61 (Cyr61/CCN1), a secreted extracellular matrix protein, is a novel proinflammatory factor. In this dataset skin samples from normal donors and psoriasis vulgaris patients were examined the expression of Cyr61 and IL-8 using immunohistochemistry. IMQ-induced psoriasis-like mice were treated with anti-Cyr61monoclonal antibodies (mAb)

CCN1, a Pro-Inflammatory Factor, Aggravates Psoriasis Skin Lesions by Promoting Keratinocyte Activation

Psoriasis is a common chronic skin disease characterized by epidermal hyperplasia and inflammation. The pathogenesis of psoriasis is multifactorial and is not fully understood. Here we demonstrate that CCN1 (also called Cyr61, which is short for cysteine-rich 61), an extracellular matrix protein that is also considered a pro-inflammatory factor, is highly expressed in the lesional skin of psoriasis patients, as well as in that of imiquimod (IMQ)- and IL-23-treated psoriasis-like mice. Then we show that blocking CCN1 function in vivo attenuates epidermal hyperplasia and inflammation in psoriasis-like mice. Further, in primary cultured normal human keratinocytes and HaCaT (human keratinocyte cell line) cells, CCN1 promotes keratinocyte activation, including the proliferation and expression of immune-related molecules. Finally, we observe that integrin α6β1 is the receptor of CCN1 in keratinocytes, and CCN1 stimulation activates the downstream phosphoinositide-3 kinase/Akt/NF-κB signaling pathway. Taken together, our findings reveal that CCN1 has a critical role in psoriasis pathogenesis. Moreover, as CCN1 is a secreted extracellular matrix (ECM) protein, our study also provides evidence that ECM, which is involved in psoriatic pathogenesis, could be a potent target for psoriasis treatment