Biomedical subjects

Chang-Yi Cui

Publications and source records attributed to Chang-Yi Cui.

7 recordsLinked to original sources

PubMed2026

Macrophage regulation of extracellular matrix remodeling in aging skeletal muscle.

The extracellular matrix (ECM) is a dynamic structural network that supports tissue architecture and regulates cell function. It is primarily composed of collagens, elastin, proteoglycans, and glycoproteins, which are synthesized by canonical and non-canonical ECM-producing cells. During aging, the ECM undergoes progressive changes in structure and composition, a process recently recognized as the 13th hallmark of aging. In skeletal muscle (SKM), age-associated ECM remodeling, largely regulated by immune system-ECM crosstalk, contributes to sarcopenia and impaired regeneration. Macrophages (MΦs), as key innate immune cells, regulate ECM dynamics both indirectly by activating canonical ECM-producing cells and directly by synthesizing ECM components. Notably, a distinct subset of ECM-producing MΦs that express collagen (COL+ MΦs) has been identified across multiple tissues, although their function in SKM homeostasis and aging remains poorly understood. Here, we review current knowledge of ECM production and remodeling, with special emphasis on MΦ involvement, including COL+ MΦs, as critical regulators of fibrogenesis, especially during SKM aging and regeneration.

Extracellular Matrix↗

PubMed2006

EDA signaling and skin appendage development.

The same morphogenetic signals are often involved in the development of different organs. For developing skin appendages, a model for tissue-specific regulation of signaling is provided by the EDA pathway, which accesses the otherwise ubiquitous NFkappaB transcription factors. EDA signaling is mediated by ectodysplasin, EDAR and EDARADD, which form a new TNF ligand-receptor-adaptor family that is restricted to skin appendages in vertebrates from fish to human. The critical function of the pathway was demonstrated in the hereditary genetic disorder Anhidrotic Ectodermal Dysplasia (EDA), which is characterized by defective formation of hair follicles, sweat glands and teeth. The pathway does not appear to initiate the development of the appendages, but is regulated by and regulates the course of further morphogenesis. In mice, transgenic and knockout strains have increasingly revealed features of the mechanism, and suggest possible non-invasive interventions to alleviate EDA deficiency, especially in sweat glands and eyes.

Amino Acid Sequence↗

PubMed2006

Ectodysplasin regulates the lymphotoxin-beta pathway for hair differentiation.

Mutations in the EDA gene cause anhidrotic/hypohidrotic ectodermal dysplasia, a disorder characterized by defective formation of hair, sweat glands, and teeth in humans and in a mouse model, "Tabby" (Ta). The gene encodes ectodysplasin, a TNF ligand family member that activates the NF-kappaB-signaling pathway, but downstream targets and the mechanism of skin appendage formation have been only partially analyzed. Comparative transcription profiling of embryonic skin during hair follicle development in WT and Ta mice identified critical anhidrotic/hypohidrotic ectodermal dysplasia (EDA) effectors in four pathways, three already implicated in follicle formation. They included Shh and its effectors, as well as antagonists for the Wnt (Dkk4) and BMP (Sostdc1) pathways. The fourth pathway was unexpected, a variant NF-kappaB-signaling cascade based on lymphotoxin-beta (LTbeta)/RelB. Previously known to participate only in lymphoid organogenesis, LTbeta was enriched in developing hair follicles of WT but not in Ta mice. Furthermore, in mice lacking LTbeta, all three types of mouse hair were still formed, but all were structurally abnormal. Guard hairs became wavy and irregular, zigzag/auchen hairs lost their kinks, and in a phenocopy of features of Ta animals, the awl hairs doubled in number and were characteristically distorted and pinched. LTbeta-null mice that received WT bone marrow transplants maintained mutant hair phenotypes, consistent with autonomous LTbeta action in skin independent of its expression in lymphoid cells. Thus, as an EDA target, LTbeta regulates the form of hair in developing hair follicles; and when EDA is defective, failure of LTbeta activation can account for part of the Ta phenotype.

Animals↗

PubMed2006

Repertoire of mouse ectodysplasin-A (EDA-A) isoforms.

Mutations in ectodysplasin-A (EDA) cause loss of hair, sweat glands, and teeth in man and mouse. Isoform EDA-A1 protein shows partial rescue of the affected Tabby mouse phenotypes, suggesting that other isoforms may be required for full function. We describe genomic structure for five EDA isoforms, EDA-A1', A5, A5', A6, and A6', in addition to the previously known EDA-A1, A2, A3, and A4. The novel isoforms together account for approximately 12% of total EDA transcripts. The most different, EDA-A6 and A6', which lack the critical domain for interaction with NF-kappaB-activating receptors, were nevertheless confirmed to be present in mouse and human skin tissue. Other isoforms, EDA-A5 and A5', for example, activated NF-kappaB through receptors EDAR and XEDAR. These properties make new isoforms candidates for modulators of EDA function.

Animals↗

PubMed2005

X-linked anhidrotic ectodermal dysplasia disruption yields a mouse model for ocular surface disease and resultant blindness.

X-linked anhidrotic/hypohidrotic ectodermal dysplasia (EDA) is caused by mutations in the (EDA) gene, which is required for the morphogenesis of ectoderm-derived tissues. Although EDA function in skin appendage development has been studied in Eda mutant "Tabby" mice, we have recently identified characteristic abnormalities in the ocular surface, an ectoderm-derived tissue. Histology of eyes of Tabby males revealed that 1) as previously reported, mice lacked meibomian glands; 2) >80% developed corneal lesions such as neovascularization, keratitis, ulceration, and keratinization identifiable from 9 weeks of age; and 3) > 80% showed ocular surface inflammation (blepharitis and conjunctivitis) when housed in a standard environment. Strikingly, both corneal defects and inflammation were prevented in Tabby mice bearing a transgene for the Eda-A1 isoform, but meibomian glands were restored little if at all. These findings suggest that intact ocular surface health is EDA dependent and that Tabby corneal abnormalities are not solely dependent on meibomian gland lipid secretion. Alternatively, susceptibility to inflammation and other phenotypes could result from failure of the usual EDA receptor to activate nuclear factor-kappaB transcription factors. This can be further tested in Tabby and Tabby-EDA transgenic mice, which provide unique models of severe ocular surface disease.

Animals↗

PubMed2003

Inducible mEDA-A1 transgene mediates sebaceous gland hyperplasia and differential formation of two types of mouse hair follicles.

EDA splice isoforms EDA-A1 and EDA-A2 belong to the TNF ligand family and regulate skin appendage formation by activating NF-kappa B- and JNK- promoted transcription. To analyze their action further, we conditionally expressed the isoforms as tetracycline ('Tet')-regulated transgenes in Tabby (EDA-negative) and wild-type mice. Expression of only the mEDA-A1 transgene had two types of effects during embryogenesis: (1) determinative effects on sweat glands and hair follicles. In Tabby mice, one type of hair follicle ('guard hair') was restored, whereas a second type, the dominant undercoat hair follicle ('zigzag') was not; furthermore, the transgene sharply suppressed zigzag hair formation in wild-type mice, with the overall numbers of back hair follicles remaining the same; and (2) trophic effects on sebaceous and Meibomian glands. Marked hyperplasia resulted from expansion of the sebocyte-producing zone in sebaceous glands, with particularly high expression of the transgene and the replication marker PCNA, and correspondingly high production of sebum. The phenotypic effects of mEDA-A1 on sebaceous glands, but not on hair follicles, were reversed when the gene was repressed in adult animals. The results thus reveal both initiating and trophic isoform-specific effects of the EDA gene, and suggest a possible balance of isoform interactions in skin appendage formation.

Animals↗

PubMed2002

EDA targets revealed by skin gene expression profiles of wild-type, Tabby and Tabby EDA-A1 transgenic mice.

Mutations in the EDA gene cause anhidrotic ectodermal dysplasia (EDA), with lesions in skin appendage formation. To begin to analyze EDA pathways, we have used expression profiling on 15,000-gene mouse cDNA microarrays, comparing adult mouse skin from wild-type, EDA-defective (Tabby) mice, and Tabby mice supplemented with the EDA-A1 isoform, which is sufficient to rescue multiple Tabby phenotypes. Given the sensitivity of the current microarray system, 8500 genes (60%) were estimated to be expressed, including transcription factors and growth-regulatory genes that had not previously been identified in skin; but only 24 (0.16%), one-third of them novel, showed significant differences between wild type and Tabby. An additional eight genes not included in the 15,000 gene set were shown to have expression differences by real-time RT-PCR. Sixteen of 32 affected genes were restored significantly toward wild-type levels in EDA-A1 transgenic Tabby mice. Significant up-regulation in Tabby skin was observed for several dermal matrix genes, including Col1a1, Col1a2, Col3a1 and SPARC: In contrast, down-regulation occurred for the NEMO/NF-kappa B pathway, already implicated in skin appendage formation, and even more markedly for a second pathway, JNK/c-jun/c-fos and their target genes, that has not previously been clearly associated with skin development. These data are consistent with the regulation of the NF-kappa B pathway by EDA, and support its involvement in the regulation of the JNK pathway as well.

Animals↗