Epidermal PPARγ Is a Key Homeostatic Regulator of Cutaneous Inflammation and Barrier Function in Mouse Skin.
Epidermal PPARγ Is a Key Homeostatic Regulator of Cutaneous Inflammation and Barrier Function in Mouse Skin.
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DOI：
10.3390/ijms22168634
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发表时间：
2021-08-11
影响因子：
5.6
通讯作者：
Turner MJ
中科院分区：
文献类型：
--
作者：
Konger RL;Derr-Yellin E;Zimmers TA;Katona T;Xuei X;Liu Y;Zhou HM;Simpson ER Jr;Turner MJ
激动剂研究和功能丧失模型均表明，PPAR γ在皮肤生物学中起重要作用。由于PPAR γ具有高水平的基础活性，我们假设表皮PPAR γ将调节表皮内的正常稳态过程。在本研究中，我们对基因敲除小鼠和野生型同窝小鼠的表皮刮片进行了mRNA测序和差异表达分析。Pparg-/-epi小鼠在14，482个鉴定的转录物中的11.8%的表达中表现出1.5倍或更大的变化。上调的转录物包括大量细胞因子/趋化因子及其受体的转录物，以及与炎性小体活化和角化相关的基因。Pparg-/-epi小鼠皮肤中最显著上调的几个促炎基因包括Igfl3、2610528A11Rik和Il1f6。从非病变全层皮肤获得的RNA进行RT-PCR，并证实这些转录物以及编码Igfl3受体的Igflr1和2610528A11Rik受体（Gpr15）的转录物显著增加。在Pparg-/-epi小鼠皮肤中检测到Il4的转录物，但未检测到Il17和Il22的转录物。下调的转录物包括皮脂腺标记物和一些与脂质屏障形成相关的基因。这些转录本的变化与痤疮表型、经表皮水分流失增加、脱发、头皮屑和自发性炎症性皮肤病变的出现相关。组织学上，非病变皮肤表现为角化过度，而炎性病变的特征在于真皮炎症和表皮棘层增生、海绵状增生和角化不全。总之，表皮Pparg的缺失改变了与皮肤炎症、角化和皮脂腺功能相关的大量基因。这些数据表明，表皮PPAR γ在稳态表皮功能中起重要作用，特别是表皮分化、屏障功能、皮脂腺发育和功能以及炎症信号传导。
Both agonist studies and loss-of-function models indicate that PPARγ plays an important role in cutaneous biology. Since PPARγ has a high level of basal activity, we hypothesized that epidermal PPARγ would regulate normal homeostatic processes within the epidermis. In this current study, we performed mRNA sequencing and differential expression analysis of epidermal scrapings from knockout mice and wildtype littermates. Pparg-/-epi mice exhibited a 1.5-fold or greater change in the expression of 11.8% of 14,482 identified transcripts. Up-regulated transcripts included those for a large number of cytokines/chemokines and their receptors, as well as genes associated with inflammasome activation and keratinization. Several of the most dramatically up-regulated pro-inflammatory genes in Pparg-/-epi mouse skin included Igfl3, 2610528A11Rik, and Il1f6. RT-PCR was performed from RNA obtained from non-lesional full-thickness skin and verified a marked increase in these transcripts, as well as transcripts for Igflr1, which encodes the receptor for Igfl3, and the 2610528A11Rik receptor (Gpr15). Transcripts for Il4 were detected in Pparg-/-epi mouse skin, but transcripts for Il17 and Il22 were not detected. Down-regulated transcripts included sebaceous gland markers and a number of genes associated with lipid barrier formation. The change in these transcripts correlates with an asebia phenotype, increased transepidermal water loss, alopecia, dandruff, and the appearance of spontaneous inflammatory skin lesions. Histologically, non-lesional skin showed hyperkeratosis, while inflammatory lesions were characterized by dermal inflammation and epidermal acanthosis, spongiosis, and parakeratosis. In conclusion, loss of epidermal Pparg alters a substantial set of genes that are associated with cutaneous inflammation, keratinization, and sebaceous gland function. The data indicate that epidermal PPARγ plays an important role in homeostatic epidermal function, particularly epidermal differentiation, barrier function, sebaceous gland development and function, and inflammatory signaling.
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DOI：
10.1161/atvbaha.112.300962
发表时间：
2013-04-01
影响因子：
8.7
作者：
Auclair, Martine;Vigouroux, Corinne;Caron-Debarle, Martine
通讯作者：
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DOI：
10.1073/pnas.2536828100
发表时间：
2003-12-23
影响因子：
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