Dongsheng Jiang

• Ph.D.
• PI and group leader at Shanghai General Hospital

Mesenchymal stem cells (MSCs) are crucial for tissue homeostasis and regeneration. Though of prime interest, their potentially protective role on neutrophil-induced tissue damage, associated with high morbidity and mortality, has not been explored in sufficient detail. Here we report the therapeutic skill of MSCs to suppress unrestrained neutrophil...

During fetal development, mammalian back-skin undergoes a natural transition in response to injury, from scarless regeneration to skin scarring. Here, we characterize dermal morphogenesis and follow two distinct embryonic fibroblast lineages, based on their history of expression of the engrailed 1 gene. We use single-cell fate-mapping, live three d...

Mammals form scars to quickly seal wounds and ensure survival by an incompletely understood mechanism1–5. Here we show that skin scars originate from prefabricated matrix in the subcutaneous fascia. Fate mapping and live imaging revealed that fascia fibroblasts rise to the skin surface after wounding, dragging their surrounding extracellular jelly-...

Scars are more severe when the subcutaneous fascia beneath the dermis is injured upon surgical or traumatic wounding. Here, we present a detailed analysis of fascia cell mobilisation by using deep tissue intravital live imaging of acute surgical wounds, fibroblast lineage-specific transgenic mice, and skin-fascia explants (scar-like tissue in a dis...

The origins of wound myofibroblasts and scar tissue remains unclear, but it is assumed to involve conversion of adipocytes into myofibroblasts. Here, we directly explore the potential plasticity of adipocytes and fibroblasts after skin injury. Using genetic lineage tracing and live imaging in explants and in wounded animals, we observe that injury...

Although the therapeutic potential of microRNA-mediated gene regulation has been investigated, its precise functional regulatory mechanism in neuropathic pain remains incompletely understood. In this study, we elucidate that miR-216a-3p serves as a critical noncoding RNA involved in the modulation of trigeminal-mediated neuropathic pain. By conduct...

The N6-methyladenosine (m ⁶ A) modification of RNA is an emerging epigenetic regulatory mechanism that has been shown to participate in various pathophysiological processes. However, its involvement in modulating neuropathic pain is still poorly understood. In this study, we elucidate a functional role of the m ⁶ A demethylase alkylation repair hom...

The transient receptor potential vanilloid 4 (TRPV4) specifically functions as a mechanosensitive ion channel and is responsible for conveying changes in physical stimuli such as mechanical stress, osmotic pressure, and temperature. TRPV4 enables the entry of cation ions, particularly calcium ions, into the cell. Activation of TRPV4 channels initia...

Optimal tissue recovery and organismal survival are achieved by spatiotemporal tuning of tissue inflammation, contraction and scar formation¹. Here we identify a multipotent fibroblast progenitor marked by CD201 expression in the fascia, the deepest connective tissue layer of the skin. Using skin injury models in mice, single-cell transcriptomics a...

Although beta-endorphinergic neurons in the hypothalamic arcuate nucleus (ARC) synthesize beta-endorphin (β-EP) to alleviate nociceptive behaviors, the underlying regulatory mechanisms remain unknown. Here, we elucidated an epigenetic pathway driven by microRNA regulation of β-EP synthesis in ARC neurons to control neuropathic pain. In pain-injured...

Chronic wounds are characterized by delayed and dysregulated healing processes. As such, they have emerged as an increasingly significant threat. The associated morbidity and socioeconomic toll are clinically and financially challenging, necessitating novel approaches in the management of chronic wounds. Metal‐organic frameworks (MOFs) are an innov...

Background Adipokines, including adiponectin, are implicated in nociceptive pain; however, the underlying cellular and molecular mechanisms remain unknown. Methods Using electrophysiological recording, immunostaining, molecular biological approaches and animal behaviour tests, we elucidated a pivotal role of adiponectin in regulating membrane exci...

Injuries to our skin trigger a cascade of spatially- and temporally-synchronized healing processes. During such endogenous wound repair, the role of fibroblasts is multifaceted, ranging from the activation and recruitment of innate immune cells through the synthesis and deposition of scar tissue to the conveyor belt-like transport of fascial connec...

The increasingly aging society led to a rise in the prevalence of chronic wounds (CWs), posing a significant burden to public health on a global scale. One of the key features of CWs is the presence of a maladjusted immune microenvironment characterized by persistent and excessive (hyper)inflammation. A variety of immunomodulatory therapies have be...

Diabetic wounds are characterized by drug‐resistant bacterial infections, biofilm formation, impaired angiogenesis and perfusion, and oxidative damage to the microenvironment. Given their complex nature, diabetic wounds remain a major challenge in clinical practice. Reactive oxygen species (ROS), which have been shown to trigger hyperinflammation a...

Deep skin wounds rapidly heal by mobilizing extracellular matrix and cells from the fascia, deep beneath the dermal layer of the skin, to form scars. Despite wounds being an extensively studied area and an unmet clinical need, the biochemistry driving this patch-like repair remains obscure. Lacking also are efficacious therapeutic means to modulate...

Wound healing disorders are a societal, clinical, and healthcare burden and understanding and treating them is a major challenge. A particularly important cell type in the wound healing processes is the fibroblast. Fibroblasts are not homogenous; however, there are diverse functional fibroblast subtypes coming from different embryonic origins and r...

Skin wound repair has been the central focus of clinicians and scientists for almost a century. Insights into acute and chronic wound healing as well as scarring have influenced and ameliorated wound treatment. Our knowledge of normal skin notwithstanding, little is known of acute and chronic wound repair of genital skin. In contrast to extra-genit...

Significance In this study, we identify microRNA-32-5p (miR-32-5p) as a key functional noncoding RNA in trigeminal-mediated neuropathic pain. We report that injury-induced histone methylation attenuates the binding of glucocorticoid receptor to the promoter region of the miR-32-5p gene and decreases the expression of miR-32-5p, in turn promoting th...

Extravasation of monocytes into tissue and to the site of injury is a fundamental immunological process, which requires rapid responses via post translational modifications (PTM) of proteins. Protein arginine methyltransferase 7 (PRMT7) is an epigenetic factor that has the capacity to mono-methylate histones on arginine residues. Here we show that...

Background: Interleukin-33 (IL-33) has been implicated in nociceptive pain behaviors. However, the underlying molecular and cellular mechanisms remain unclear. Methods: Using electrophysiological recording, immunoblot analysis, immunofluorescence labeling, reverse transcription-PCR, siRNA-mediated knockdown approach and behavior tests, we determine...

The skin is home to a collection of fibroblastic cell types from varying embryonic origins. These varying fibroblastic lineages display unique genetic programs and in vivo functions. Studying the diversity of fibroblastic cells is emerging as an important area for cutaneous biology, wound repair and regenerative medicine. In this mini-review we dis...

Background: Neuromedin B (Nmb) is implicated in the regulation of nociception of sensory neurons. However, the underlying cellular and molecular mechanisms remain unknown. Methods: Using patch clamp recording, western blot analysis, immunofluorescent labelling, enzyme-linked immunosorbent assays, adenovirus-mediated shRNA knockdown and animal behav...

Mammals rapidly heal wounds through fibrous connective tissue build up and tissue contraction. Recent findings from mouse attribute wound healing to physical mobilization of a fibroelastic connective tissue layer that resides beneath the skin, termed subcutaneous fascia or superficial fascia, into sites of injury. Fascial mobilization assembles div...

Fibroblastic stromal cells are as diverse, in origin and function, as the niches they fashion in the mammalian body. This cellular variety impacts the spectrum of responses elicited by the immune system. Fibroblast influence on the immune system keeps evolving our perspective on fibroblast roles and functions beyond just a passive structural part o...

Deep and voluminous skin wounds are repaired with scars, by mobilization of fibroblasts and extracellular matrix from fascia, deep below the skin. The molecular trigger of this novel repair mechanism is incompletely understood. Here we reveal that the gap junction alpha-1 protein (Connexin43, Cx43) is the key to patch repair of deep wounds. By comb...

Aim: Scarring is a physiological process in adult wound repair. Although keratinocytes and fibroblasts are the main cell types of the skin, they differ in migration behaviour and inflammatory responses depending on their location in the body. The aim of this article is to describe wound repair in genital skin and to depict differences with regard t...

Granulation tissue formation constitutes a key step during wound healing of the skin and other organs. Granulation tissue concomitantly initiates regenerative M2 macrophages polarization, fibroblast proliferation, myofibroblast differentiation with subsequent contraction of the wound, new vessel formation, and matrix deposition. Impaired granulatio...

We here address the question whether the unique capacity of mesenchymal stem cells to re-establish tissue homeostasis depends on their potential to sense pathogen-associated molecular pattern and, in consequence, mount an adaptive response in the interest of tissue repair. After injection of MSCs primed with the bacterial wall component LPS into mu...

Mutations in the CD18 gene encoding the common β-chain of β2 integrins result in impaired wound healing in humans and mice suffering from leukocyte adhesion deficiency syndrome type 1 (LAD1). Transplantation of adipose tissue-derived mesenchymal stem cells (MSCs) restores normal healing of CD18-/- wounds by restoring the decreased TGF-β1 concentrat...

Scarring and regeneration are two physiologically opposite endpoints to skin injuries, with mammals, including humans, typically healing wounds with fibrotic scars. We aim to provide an updated review on fibroblast heterogeneity as determinants of the scarring–regeneration continuum. We discuss fibroblast-centric mechanisms that dictate scarring–re...

Background: Cholecystokinin (CCK) is implicated in the regulation of nociceptive sensitivity of primary afferent neurons. Nevertheless, the underlying cellular and molecular mechanisms remain unknown. Methods: Using patch clamp recording, western blot analysis, immunofluorescent labelling, enzyme-linked immunosorbent assays, adenovirus-mediated...

Non‐healing chronic wounds in the constantly growing elderly population represent a major public health problem with high socio‐economic burden. Yet the underlying mechanism of age‐related impairment of wound healing remains elusive. Here we show that the number of dermal cells expressing cyclin dependent kinase inhibitor p21 was elevated upon skin...

Although brain-derived neurotrophic factor (BDNF) is implicated in the nociceptive signaling of peripheral sensory neurons, the underlying mechanisms remain largely unknown. Here, we elucidated the effects of BDNF on the neuronal excitability of trigeminal ganglion (TG) neurons and the pain sensitivity of rats mediated by T-type Ca ²⁺ channels. BDN...

Here we report the beneficial effects of a newly identified dermal cell subpopulation expressing the ATP-binding cassette subfamily B member 5 (ABCB5) for the therapy of non-healing wounds. Local administration of dermal ABCB5+ -derived MSCs attenuated macrophage-dominated inflammation and thereby accelerated healing of full-thickness excisional wo...

Alpha-melanocyte–stimulating hormone (α-MSH) has been shown to be involved in nociception, but the underlying molecular mechanisms remain largely unknown. In this study, we report that α-MSH suppresses the transient outward A-type K⁺ current (IA) in trigeminal ganglion (TG) neurons and thereby modulates neuronal excitability and peripheral pain sen...

Neutrophils are the most abundant leukocytes in the blood. In the recent decades, their crucial roles in host defense, immune regulation and tissue damage have been studied in a deeper dimension. In this protocol, we described a mouse model of immune complex-mediated vasculitis in the dorsal skin induced by Arthus reaction, and the subsequent analy...

In the recent decade, neutrophil extracellular traps (NETs) have been identified and confirmed as a new anti-microbial weapon of neutrophils. In this protocol, we describe easy methods to demonstrate NET formation by immunofluorescence staining of extracellular chromatin fiber with anti-DNA/Histone H1 antibody and quantification of NETs by using a...

Diabetes is a debilitating, life-threatening disease accounting in 2015 for the death of 5 million people worldwide. According to new estimations, 415 million adults currently suffer from the disease, and this number is expected to rise to 642 million by 2040. High glucose blood levels also affect the skin among systemic organs, and skin disorders...

Poster 577 at the 46th Annual ESDR Meeting 2016 - Munich, Germany (7-10 September 2016)

Murine macrophage NADPH oxidase controls wound healing A Kügler,1 S Schatz,1 S Vander Beken,1 D Jiang,1 T Peters,1 L Schneider,1 A Rück,2 B De Geest,3 K Scharffetter-Kochanek1 and A Sindrilaru1 1 Dermatology and Allergic Diseases, University of Ulm, Ulm, Germany, 2 Core Facility for Confocal and Multiphoton Microscopy, University of Ulm, Ulm, Ge...

Wound healing and scar remodelling are complex, multi-cellular processes that involve coordinated regulation of many cell types and various cytokines. The repair capacity gradually decreases with aging, constituting a severe health problem that frequently affects aged individuals. The decrease in cell number and function of mesenchymal stem cells (...

Towards further characterization of ABCB5+ mesenchymal stem cells in the ageing skin J. C. de Vries1, B. Meier1, D. Jiang1, N. Y. Frank2,3, S. Vander Beken1, Y. Ziouta4, A. Kluth4,C. Ganss4, M. H. Frank2,3 and K. Scharffetter-Kochanek1 1Department of Dermatology and Allergic Diseases, University of Ulm, 89081 Ulm, Germany; 2Harvard Medical School,...

IL-1 signalling is up-regulated in chronic venous leg ulcers and represents a therapeutic target that is counteracted by dermal ABCB5+ mesenchymal stem cells via secretion of interleukin-1 receptor antagonist S. Vander Beken1, P. Meyer1, A. Sindrilaru1, D. Jiang1, J. C. de Vries1, S. Schatz1, A. Heinzl1, A. Kluth2, B. Over2, S. Miller3, N. Kettern3...

Recent studies have demonstrated that urotensin-II (U-II) plays important roles in cardiovascular actions including cardiac positive inotropic effects and increasing cardiac output. However, the mechanisms underlying these effects of U-II in cardiomyocytes remain still unknown. We show by electrophysiological studies that U-II dose-dependently pote...

Wound healing and scar remodeling are complex, multicellular processes that involve coordinated regulation of many cell types andvarious cytokines. The repair capacity gradually decreases with aging, constituting a severe health problem that frequently affects aged individuals. The decrease in cell number and function of mesenchymal stem cells (MSC...

Neutrophils, as the first cellular line of innate host defense, employ phagocytosis and formation of neutrophil extracellular traps (NETs) to combat infections. Classical NET formation induced by phorbol myristate acetate requires several hours to complete. However, recent studies demonstrated rapid NET formation in neutrophils upon stimulation by...

CD137 ligand (CD137L) has emerged as a powerful regulator of myelopoiesis that links emergency situations, such as infections, to the generation of additional myeloid cells, and to their activation and maturation. CD137L is expressed on the cell surface of hematopoietic stem and progenitor cells (HSPC) and antigen presenting cells (APC) as a transm...

Alveolar type II cells (ATII cells) are lung progenitor cells responsible for regeneration of alveolar epithelium during homeostatic turnover and in response to injury. Characterization of ATII cells will have a profound impact on our understanding and treatment of lung disease. The identification of novel ATII cell surface proteins can be used for...

CD137 is a costimulatory molecule expressed on activated T cells. Its ligand, CD137L, is expressed on the surface of hematopoietic progenitor cells, and upon binding to CD137 induces reverse signaling into hematopoietic progenitor cells promoting their activation, proliferation and myeloid differentiation. Since aging is associated with an increasi...

Proper activation of macrophages in the inflammatory phase of acute wound healing is essential for physiologic tissue repair. However, there is strong indication that robust macrophage inflammatory responses may be causal for the fibrotic response always accompanying adult wound healing. Using a complementary approach of in vitro and in vivo studie...

CD137 and its ligand are expressed in the bone marrow, and conflicting data exist on the regulation of myelopoiesis by the CD137 receptor- ligand system. CD137(-/-) mice have increased numbers of myeloid cells in the bone marrow, indicating an inhibitory influence of CD137 on myelopoiesis. However, CD137 also induces proliferation of hematopoietic...

Although neuromedin U (NMU) has been implicated in analgesia, the detailed mechanisms still remain unclear. In this study, we identify a novel functional role of NMU type 1 receptor (NMUR1) in regulating the transient outward K+ currents (IA) in small dorsal root ganglion (DRG) neurons. We found that NMU reversibly increased IA in a dose-dependent...

Endostatin (ES) is a c-terminal proteolytic fragment of collagen XVIII with promising antitumour properties in several tumour models, including human glioblastoma. We hypothesized that this peptide could interact with plasma membrane ion channels and modulate their functions. Using cell proliferation and migration assays, patch clamp and Western bl...

High macrophage infiltration into tumours often correlates with poor prognoses; in colorectal, stomach and skin cancers, however, the opposite is observed but the mechanisms behind this phenomenon remain unclear. Here, we sought to understand how tumour-associated macrophages (TAMs) in colorectal cancer execute tumour-suppressive roles. We found th...

The long-chain neurotoxic protein, alpha-cobratoxin (α-CTx), has been shown to have analgesic effects. However, the underlying mechanisms still remain unclear. In this study, we examined the effects of α-CTx on T-type calcium channel currents (T-currents) and elucidated the relevant mechanisms in mouse dorsal root ganglion (DRG) neurons. Our result...

Ghrelin, a newly isolated brain-gut peptide, has been found to play important roles in the male reproduction. However, to date, the detailed mechanisms still remain unknown. In this study, we identified a novel functional role of ghrelin in modulating T-type Ca(2+) channel currents (T-currents) in mouse spermatogenic cells. We found that ghrelin in...

Stimulation of CD137 ligand on human monocytes has been shown to induce DC differentiation, and these CD137L-DCs are more potent than classical DCs, in stimulating T cell responses in vitro. To allow an in vivo evaluation of the potency of CD137L-DCs in murine models we aimed at generating murine CD137L-DCs. When stimulated through CD137 ligand mur...

CD137 and CD137 ligand are members of the tumor necrosis factor (TNF) receptor and TNF family, respectively. CD137 is expressed by cells in the bone marrow and CD137 ligand is expressed on hematopoietic progenitor cells. The interaction of CD137 and CD137 ligand induced proliferation and colony formation of hematopoietic progenitor cells and their...

Granulocytes and monocytes/macrophages differentiate from common myeloid progenitor cells. Granulocyte colony-stimulating factor (G-CSF) and CD137 (4-1BB, TNFRSF9) are growth and differentiation factors that induce granulocyte and macrophage survival and differentiation, respectively. This study describes the influence of G-CSF and recombinant CD13...

Neuromedin U (NMU) plays very important roles in the central nervous system. However, to date, any role of NMU in hippocampal neurons and the relevant mechanisms still remain unknown. In the present study, we report that NMU selectively inhibits L-type high-voltage-gated Ca(2+) channels (HVGCC) in mouse hippocampal neurons, in which NMU type 1 rece...

CD137 is a member of the TNFR family, and reverse signaling through the CD137 ligand, which is expressed as a cell surface transmembrane protein, costimulates or activates APCs. CD137 and CD137 ligand are expressed on small subsets of bone marrow cells. Activation of bone marrow cells through CD137 ligand induces proliferation, colony formation and...

CD137 is a member of the tumor necrosis factor receptor family and is involved in the regulation of activation, proliferation, differentiation, and cell death of leukocytes. Bidirectional signaling exists for the CD137 receptor/ligand system, as CD137 ligand, which is expressed as a transmembrane protein, can also transduce signals into the cells o...