RESUMO
The hair follicle and nail unit develop and regenerate through epithelial-mesenchymal interactions. Here, we review some of the key signals and molecular interactions that regulate mammalian hair follicle and nail formation during embryonic development and how these interactions are reutilized to promote their regeneration during adult homeostasis and in response to skin wounding. Finally, we highlight the role of some of these signals in mediating human hair follicle and nail conditions.
Assuntos
Folículo Piloso , Unhas , Folículo Piloso/embriologia , Humanos , Unhas/embriologia , Unhas/crescimento & desenvolvimento , Animais , Transdução de Sinais , Regeneração/fisiologiaRESUMO
This study explored the legacy impact of Zinc plant residues (ZPRs) in Kabwe, Zambia, on the environment and human health, particularly in light of the town's reputation for Pb pollution. ZPRs solid samples and groundwater within and around ZPRs zone were collected from the legacy mine, along with soils in a 10 km radius from the mine site. Bioaccessible fractions of Pb and Zn were elucidated by Japanese leaching test (JLT) and simple bioaccessibility extraction test (SBET). Cationic speciation of Pb and Zn from inhalable and ingestible ZPRs particles was investigated via sequential extraction. Groundwater in the ZPRs area showed higher Zn levels (1490 mg/L) compared to Pb (1.7 mg/L). Elevated Zn concentration were facilitated by the presence of soluble Zn sulfates while Pb was constrained due to its precipitation as anglesite. Groundwater sampled outside the ZPRs area was within the Zambia regulatory limits (< 0.5 mg/L for Pb and < 1 mg/L for Zn). Inhalation exposure to < 30 µm dust particles from ZPRs and soils near the mine indicated negligible risk, with < 3% of bioaccessible Pb in artificial lysosomal fluid. Meanwhile, oral intake of ZPRs particles < 250 µm revealed elevated bioaccessible fractions (36% for Pb and 70% for Zn). ZPRs cationic speciation of ingestible particles < 30 µm, 30-75 µm, 75-150 µm and 150-250 µm indicated that the bioaccessible Pb predominantly emanated from labile Pb fractions under gastric conditions with pH < 1. This was due to the dissolution of Pb associated with the exchangeable phase, carbonates and iron/manganese oxides; however, only exchangeable/carbonate Pb was bioaccessible at pH < 2. Hazard quotients indicated increased risks of Pb intoxication through the ingestion of ZPRs and soils near the legacy mine, with higher risks observed in children, emphasizing the need to remediate legacy mine wastes to reduce health risks and protect groundwater through monitoring in mining-affected regions.
Assuntos
Água Subterrânea , Chumbo , Criança , Humanos , Zinco , Manganês , PoeiraRESUMO
Hair follicle neogenesis (HFN) occurs after large skin excisions in mice, serving as a rare regenerative model in mammalian wound healing. Wound healing typically results in fibrosis in mice and humans. We previously showed that small skin excisions in mice result in scarring devoid of HFN, displaying features of nonregenerative healing, and hedgehog (Hh) activation in the dermis of such wounds can induce HFN. In this study, we sought to verify the role of dermal Wnt/ß-catenin signaling in HFN because this pathway is essential for hair follicle development but is also paradoxically well-characterized in fibrosis of adult wounds. By deletion of ß-catenin in large wound myofibroblasts, we show that Wnt/ß-catenin signaling is required for endogenous mechanisms of HFN. By utilizing a combined mouse model that simultaneously induces deletion of ß-catenin and constitutive activation of Smoothened in myofibroblasts, we also found that ß-catenin is required for Hh-driven dermal papilla formation. Transcriptome analysis confirms that Wnt/ß-catenin and Hh pathways are activated in dermal papilla cells. Our results indicate that Wnt-active fibrotic status may also create a permissive state for the regenerative function of Hh, suggesting that activation of both Wnt and Hh pathways in skin wound fibroblasts must be ensured in future strategies to promote HFN.
RESUMO
Em seu ambiente natural, as condições de água e temperatura são altamente variáveis, e podem afetar a sobrevivência,o crescimento e reprodução das plantas. Para sobreviver em tais condições, as plantas respondem, desenvolvendouma complexa rede de sinalização em nível molecular, celular e bioquímico. A regulação gênica em nível de transcrição éum dos principais pontos no controle dos processos biológicos, sendo que os fatores de transcrição (TFs) desempenham umpapel fundamental nesse processo. A família AP2/ERF é uma grande família de TFs específico de plantas que compartilhamum domínio conservado de ligação ao DNA. Essa família de TFs incluía proteínas da subfamília DREB que desempenhamum papel crucial na resposta das plantas a estresses abióticos, reconhecendo o elemento responsivo à desidratação com ummotivo central A/GCCGAC. As proteínas da subfamília de fatores de resposta ao etileno estão envolvidas em respostas aosestresses bióticos e abióticos, reconhecendo o elemento cis-acting AGCCGCC denominado GCC-box. Nesta revisão foi discutidoo papel dos TFs AP2/ERF em condições de estresse abiótico e suas implicações funcionais em estudos de expressãogênica. A compreensão dos determinantes genéticos da tolerância aos estresses abióticos constitui um passo importante nosprogramas de melhoramento genético.
In their natural environment, temperature and water conditions are highly variable and may affect the survival,growth and reproduction of plants. In order to survive under such conditions, plants respond by developing a complexnetwork of signaling at molecular, cellular and biochemical level. The gene regulation at the transcription level is one of themajor points in the control of biological processes, and transcription factors play a key role in this process. The AP2/ERFfamily is a large family of plant-specific transcription factors that share a conserved DNA-binding domain. This transcriptionfactor family includes a subfamily of DREB proteins that plays a crucial role in the plant response to abiotic stresses, recognizingthe dehydration responsive element with a central motif A/GCCGAC. The proteins from the subfamily of ethyleneresponse factors are involved in responses to biotic and abiotic stresses recognizing the cis-acting element AGCCGCC calledGCC-box. In this review, the authors discuss the role of AP2/ERF transcription factors in abiotic stress conditions and theirfunctional implications in gene expression studies. Understanding the genetic determinants of abiotic stress tolerance is animportant step in breeding programs.
In their natural environment, temperature and water conditions are highly variable and may affect the survival,growth and reproduction of plants. In order to survive under such conditions, plants respond by developing a complexnetwork of signaling at molecular, cellular and biochemical level. The gene regulation at the transcription level is one of themajor points in the control of biological processes, and transcription factors play a key role in this process. The AP2/ERFfamily is a large family of plant-specific transcription factors that share a conserved DNA-binding domain. This transcriptionfactor family includes a subfamily of DREB proteins that plays a crucial role in the plant response to abiotic stresses, recognizingthe dehydration responsive element with a central motif A/GCCGAC. The proteins from the subfamily of ethyleneresponse factors are involved in responses to biotic and abiotic stresses recognizing the cis-acting element AGCCGCC calledGCC-box. In this review, the authors discuss the role of AP2/ERF transcription factors in abiotic stress conditions and theirfunctional implications in gene expression studies. Understanding the genetic determinants of abiotic stress tolerance is animportant step in breeding programs constituye un paso importante en los programas de mejoramiento genético.